VCV000055441.44 - ClinVar

NM_007294.4(BRCA1):c.5165C>T (p.Ser1722Phe)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(20)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.5165C>T (p.Ser1722Phe)

Variation ID: 55441 Accession: VCV000055441.44

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43063361 (GRCh38) [ NCBI UCSC ] 17: 41215378 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 1, 2014	Jun 17, 2024	Mar 27, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.5165C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.Ser1722Phe	missense
NM_001407571.1:c.4952C>T	NP_001394500.1:p.Ser1651Phe	missense
NM_001407581.1:c.5231C>T	NP_001394510.1:p.Ser1744Phe	missense
NM_001407582.1:c.5231C>T	NP_001394511.1:p.Ser1744Phe	missense
NM_001407583.1:c.5228C>T	NP_001394512.1:p.Ser1743Phe	missense
NM_001407585.1:c.5228C>T	NP_001394514.1:p.Ser1743Phe	missense
NM_001407587.1:c.5228C>T	NP_001394516.1:p.Ser1743Phe	missense
NM_001407590.1:c.5225C>T	NP_001394519.1:p.Ser1742Phe	missense
NM_001407591.1:c.5225C>T	NP_001394520.1:p.Ser1742Phe	missense
NM_001407593.1:c.5165C>T	NP_001394522.1:p.Ser1722Phe	missense
NM_001407594.1:c.5165C>T	NP_001394523.1:p.Ser1722Phe	missense
NM_001407596.1:c.5165C>T	NP_001394525.1:p.Ser1722Phe	missense
NM_001407597.1:c.5165C>T	NP_001394526.1:p.Ser1722Phe	missense
NM_001407598.1:c.5165C>T	NP_001394527.1:p.Ser1722Phe	missense
NM_001407602.1:c.5165C>T	NP_001394531.1:p.Ser1722Phe	missense
NM_001407603.1:c.5165C>T	NP_001394532.1:p.Ser1722Phe	missense
NM_001407605.1:c.5165C>T	NP_001394534.1:p.Ser1722Phe	missense
NM_001407610.1:c.5162C>T	NP_001394539.1:p.Ser1721Phe	missense
NM_001407611.1:c.5162C>T	NP_001394540.1:p.Ser1721Phe	missense
NM_001407612.1:c.5162C>T	NP_001394541.1:p.Ser1721Phe	missense
NM_001407613.1:c.5162C>T	NP_001394542.1:p.Ser1721Phe	missense
NM_001407614.1:c.5162C>T	NP_001394543.1:p.Ser1721Phe	missense
NM_001407615.1:c.5162C>T	NP_001394544.1:p.Ser1721Phe	missense
NM_001407616.1:c.5162C>T	NP_001394545.1:p.Ser1721Phe	missense
NM_001407617.1:c.5162C>T	NP_001394546.1:p.Ser1721Phe	missense
NM_001407618.1:c.5162C>T	NP_001394547.1:p.Ser1721Phe	missense
NM_001407619.1:c.5162C>T	NP_001394548.1:p.Ser1721Phe	missense
NM_001407620.1:c.5162C>T	NP_001394549.1:p.Ser1721Phe	missense
NM_001407621.1:c.5162C>T	NP_001394550.1:p.Ser1721Phe	missense
NM_001407622.1:c.5162C>T	NP_001394551.1:p.Ser1721Phe	missense
NM_001407623.1:c.5162C>T	NP_001394552.1:p.Ser1721Phe	missense
NM_001407624.1:c.5162C>T	NP_001394553.1:p.Ser1721Phe	missense
NM_001407625.1:c.5162C>T	NP_001394554.1:p.Ser1721Phe	missense
NM_001407626.1:c.5162C>T	NP_001394555.1:p.Ser1721Phe	missense
NM_001407627.1:c.5159C>T	NP_001394556.1:p.Ser1720Phe	missense
NM_001407628.1:c.5159C>T	NP_001394557.1:p.Ser1720Phe	missense
NM_001407629.1:c.5159C>T	NP_001394558.1:p.Ser1720Phe	missense
NM_001407630.1:c.5159C>T	NP_001394559.1:p.Ser1720Phe	missense
NM_001407631.1:c.5159C>T	NP_001394560.1:p.Ser1720Phe	missense
NM_001407632.1:c.5159C>T	NP_001394561.1:p.Ser1720Phe	missense
NM_001407633.1:c.5159C>T	NP_001394562.1:p.Ser1720Phe	missense
NM_001407634.1:c.5159C>T	NP_001394563.1:p.Ser1720Phe	missense
NM_001407635.1:c.5159C>T	NP_001394564.1:p.Ser1720Phe	missense
NM_001407636.1:c.5159C>T	NP_001394565.1:p.Ser1720Phe	missense
NM_001407637.1:c.5159C>T	NP_001394566.1:p.Ser1720Phe	missense
NM_001407638.1:c.5159C>T	NP_001394567.1:p.Ser1720Phe	missense
NM_001407639.1:c.5159C>T	NP_001394568.1:p.Ser1720Phe	missense
NM_001407640.1:c.5159C>T	NP_001394569.1:p.Ser1720Phe	missense
NM_001407641.1:c.5159C>T	NP_001394570.1:p.Ser1720Phe	missense
NM_001407642.1:c.5159C>T	NP_001394571.1:p.Ser1720Phe	missense
NM_001407644.1:c.5156C>T	NP_001394573.1:p.Ser1719Phe	missense
NM_001407645.1:c.5156C>T	NP_001394574.1:p.Ser1719Phe	missense
NM_001407646.1:c.5153C>T	NP_001394575.1:p.Ser1718Phe	missense
NM_001407647.1:c.5150C>T	NP_001394576.1:p.Ser1717Phe	missense
NM_001407648.1:c.5108C>T	NP_001394577.1:p.Ser1703Phe	missense
NM_001407649.1:c.5105C>T	NP_001394578.1:p.Ser1702Phe	missense
NM_001407652.1:c.5087C>T	NP_001394581.1:p.Ser1696Phe	missense
NM_001407653.1:c.5087C>T	NP_001394582.1:p.Ser1696Phe	missense
NM_001407654.1:c.5087C>T	NP_001394583.1:p.Ser1696Phe	missense
NM_001407655.1:c.5087C>T	NP_001394584.1:p.Ser1696Phe	missense
NM_001407656.1:c.5084C>T	NP_001394585.1:p.Ser1695Phe	missense
NM_001407657.1:c.5084C>T	NP_001394586.1:p.Ser1695Phe	missense
NM_001407658.1:c.5084C>T	NP_001394587.1:p.Ser1695Phe	missense
NM_001407659.1:c.5081C>T	NP_001394588.1:p.Ser1694Phe	missense
NM_001407660.1:c.5081C>T	NP_001394589.1:p.Ser1694Phe	missense
NM_001407661.1:c.5081C>T	NP_001394590.1:p.Ser1694Phe	missense
NM_001407662.1:c.5081C>T	NP_001394591.1:p.Ser1694Phe	missense
NM_001407663.1:c.5081C>T	NP_001394592.1:p.Ser1694Phe	missense
NM_001407664.1:c.5042C>T	NP_001394593.1:p.Ser1681Phe	missense
NM_001407665.1:c.5042C>T	NP_001394594.1:p.Ser1681Phe	missense
NM_001407666.1:c.5042C>T	NP_001394595.1:p.Ser1681Phe	missense
NM_001407667.1:c.5042C>T	NP_001394596.1:p.Ser1681Phe	missense
NM_001407668.1:c.5042C>T	NP_001394597.1:p.Ser1681Phe	missense
NM_001407669.1:c.5042C>T	NP_001394598.1:p.Ser1681Phe	missense
NM_001407670.1:c.5039C>T	NP_001394599.1:p.Ser1680Phe	missense
NM_001407671.1:c.5039C>T	NP_001394600.1:p.Ser1680Phe	missense
NM_001407672.1:c.5039C>T	NP_001394601.1:p.Ser1680Phe	missense
NM_001407673.1:c.5039C>T	NP_001394602.1:p.Ser1680Phe	missense
NM_001407674.1:c.5039C>T	NP_001394603.1:p.Ser1680Phe	missense
NM_001407675.1:c.5039C>T	NP_001394604.1:p.Ser1680Phe	missense
NM_001407676.1:c.5039C>T	NP_001394605.1:p.Ser1680Phe	missense
NM_001407677.1:c.5039C>T	NP_001394606.1:p.Ser1680Phe	missense
NM_001407678.1:c.5039C>T	NP_001394607.1:p.Ser1680Phe	missense
NM_001407679.1:c.5039C>T	NP_001394608.1:p.Ser1680Phe	missense
NM_001407680.1:c.5039C>T	NP_001394609.1:p.Ser1680Phe	missense
NM_001407681.1:c.5036C>T	NP_001394610.1:p.Ser1679Phe	missense
NM_001407682.1:c.5036C>T	NP_001394611.1:p.Ser1679Phe	missense
NM_001407683.1:c.5036C>T	NP_001394612.1:p.Ser1679Phe	missense
NM_001407684.1:c.5165C>T	NP_001394613.1:p.Ser1722Phe	missense
NM_001407685.1:c.5036C>T	NP_001394614.1:p.Ser1679Phe	missense
NM_001407686.1:c.5036C>T	NP_001394615.1:p.Ser1679Phe	missense
NM_001407687.1:c.5036C>T	NP_001394616.1:p.Ser1679Phe	missense
NM_001407688.1:c.5036C>T	NP_001394617.1:p.Ser1679Phe	missense
NM_001407689.1:c.5036C>T	NP_001394618.1:p.Ser1679Phe	missense
NM_001407690.1:c.5033C>T	NP_001394619.1:p.Ser1678Phe	missense
NM_001407691.1:c.5033C>T	NP_001394620.1:p.Ser1678Phe	missense
NM_001407692.1:c.5024C>T	NP_001394621.1:p.Ser1675Phe	missense
NM_001407694.1:c.5024C>T	NP_001394623.1:p.Ser1675Phe	missense
NM_001407695.1:c.5024C>T	NP_001394624.1:p.Ser1675Phe	missense
NM_001407696.1:c.5024C>T	NP_001394625.1:p.Ser1675Phe	missense
NM_001407697.1:c.5024C>T	NP_001394626.1:p.Ser1675Phe	missense
NM_001407698.1:c.5024C>T	NP_001394627.1:p.Ser1675Phe	missense
NM_001407724.1:c.5024C>T	NP_001394653.1:p.Ser1675Phe	missense
NM_001407725.1:c.5024C>T	NP_001394654.1:p.Ser1675Phe	missense
NM_001407726.1:c.5024C>T	NP_001394655.1:p.Ser1675Phe	missense
NM_001407727.1:c.5024C>T	NP_001394656.1:p.Ser1675Phe	missense
NM_001407728.1:c.5024C>T	NP_001394657.1:p.Ser1675Phe	missense
NM_001407729.1:c.5024C>T	NP_001394658.1:p.Ser1675Phe	missense
NM_001407730.1:c.5024C>T	NP_001394659.1:p.Ser1675Phe	missense
NM_001407731.1:c.5024C>T	NP_001394660.1:p.Ser1675Phe	missense
NM_001407732.1:c.5021C>T	NP_001394661.1:p.Ser1674Phe	missense
NM_001407733.1:c.5021C>T	NP_001394662.1:p.Ser1674Phe	missense
NM_001407734.1:c.5021C>T	NP_001394663.1:p.Ser1674Phe	missense
NM_001407735.1:c.5021C>T	NP_001394664.1:p.Ser1674Phe	missense
NM_001407736.1:c.5021C>T	NP_001394665.1:p.Ser1674Phe	missense
NM_001407737.1:c.5021C>T	NP_001394666.1:p.Ser1674Phe	missense
NM_001407738.1:c.5021C>T	NP_001394667.1:p.Ser1674Phe	missense
NM_001407739.1:c.5021C>T	NP_001394668.1:p.Ser1674Phe	missense
NM_001407740.1:c.5021C>T	NP_001394669.1:p.Ser1674Phe	missense
NM_001407741.1:c.5021C>T	NP_001394670.1:p.Ser1674Phe	missense
NM_001407742.1:c.5021C>T	NP_001394671.1:p.Ser1674Phe	missense
NM_001407743.1:c.5021C>T	NP_001394672.1:p.Ser1674Phe	missense
NM_001407744.1:c.5021C>T	NP_001394673.1:p.Ser1674Phe	missense
NM_001407745.1:c.5021C>T	NP_001394674.1:p.Ser1674Phe	missense
NM_001407746.1:c.5021C>T	NP_001394675.1:p.Ser1674Phe	missense
NM_001407747.1:c.5021C>T	NP_001394676.1:p.Ser1674Phe	missense
NM_001407748.1:c.5021C>T	NP_001394677.1:p.Ser1674Phe	missense
NM_001407749.1:c.5021C>T	NP_001394678.1:p.Ser1674Phe	missense
NM_001407750.1:c.5021C>T	NP_001394679.1:p.Ser1674Phe	missense
NM_001407751.1:c.5021C>T	NP_001394680.1:p.Ser1674Phe	missense
NM_001407752.1:c.5021C>T	NP_001394681.1:p.Ser1674Phe	missense
NM_001407838.1:c.5018C>T	NP_001394767.1:p.Ser1673Phe	missense
NM_001407839.1:c.5018C>T	NP_001394768.1:p.Ser1673Phe	missense
NM_001407841.1:c.5018C>T	NP_001394770.1:p.Ser1673Phe	missense
NM_001407842.1:c.5018C>T	NP_001394771.1:p.Ser1673Phe	missense
NM_001407843.1:c.5018C>T	NP_001394772.1:p.Ser1673Phe	missense
NM_001407844.1:c.5018C>T	NP_001394773.1:p.Ser1673Phe	missense
NM_001407845.1:c.5018C>T	NP_001394774.1:p.Ser1673Phe	missense
NM_001407846.1:c.5018C>T	NP_001394775.1:p.Ser1673Phe	missense
NM_001407847.1:c.5018C>T	NP_001394776.1:p.Ser1673Phe	missense
NM_001407848.1:c.5018C>T	NP_001394777.1:p.Ser1673Phe	missense
NM_001407849.1:c.5018C>T	NP_001394778.1:p.Ser1673Phe	missense
NM_001407850.1:c.5018C>T	NP_001394779.1:p.Ser1673Phe	missense
NM_001407851.1:c.5018C>T	NP_001394780.1:p.Ser1673Phe	missense
NM_001407852.1:c.5018C>T	NP_001394781.1:p.Ser1673Phe	missense
NM_001407853.1:c.5018C>T	NP_001394782.1:p.Ser1673Phe	missense
NM_001407854.1:c.5165C>T	NP_001394783.1:p.Ser1722Phe	missense
NM_001407858.1:c.5162C>T	NP_001394787.1:p.Ser1721Phe	missense
NM_001407859.1:c.5162C>T	NP_001394788.1:p.Ser1721Phe	missense
NM_001407860.1:c.5162C>T	NP_001394789.1:p.Ser1721Phe	missense
NM_001407861.1:c.5159C>T	NP_001394790.1:p.Ser1720Phe	missense
NM_001407862.1:c.4964C>T	NP_001394791.1:p.Ser1655Phe	missense
NM_001407863.1:c.4961C>T	NP_001394792.1:p.Ser1654Phe	missense
NM_001407874.1:c.4958C>T	NP_001394803.1:p.Ser1653Phe	missense
NM_001407875.1:c.4958C>T	NP_001394804.1:p.Ser1653Phe	missense
NM_001407879.1:c.4955C>T	NP_001394808.1:p.Ser1652Phe	missense
NM_001407881.1:c.4955C>T	NP_001394810.1:p.Ser1652Phe	missense
NM_001407882.1:c.4955C>T	NP_001394811.1:p.Ser1652Phe	missense
NM_001407884.1:c.4955C>T	NP_001394813.1:p.Ser1652Phe	missense
NM_001407885.1:c.4955C>T	NP_001394814.1:p.Ser1652Phe	missense
NM_001407886.1:c.4955C>T	NP_001394815.1:p.Ser1652Phe	missense
NM_001407887.1:c.4955C>T	NP_001394816.1:p.Ser1652Phe	missense
NM_001407889.1:c.4955C>T	NP_001394818.1:p.Ser1652Phe	missense
NM_001407894.1:c.4952C>T	NP_001394823.1:p.Ser1651Phe	missense
NM_001407895.1:c.4952C>T	NP_001394824.1:p.Ser1651Phe	missense
NM_001407896.1:c.4952C>T	NP_001394825.1:p.Ser1651Phe	missense
NM_001407897.1:c.4952C>T	NP_001394826.1:p.Ser1651Phe	missense
NM_001407898.1:c.4952C>T	NP_001394827.1:p.Ser1651Phe	missense
NM_001407899.1:c.4952C>T	NP_001394828.1:p.Ser1651Phe	missense
NM_001407900.1:c.4952C>T	NP_001394829.1:p.Ser1651Phe	missense
NM_001407902.1:c.4952C>T	NP_001394831.1:p.Ser1651Phe	missense
NM_001407904.1:c.4952C>T	NP_001394833.1:p.Ser1651Phe	missense
NM_001407906.1:c.4952C>T	NP_001394835.1:p.Ser1651Phe	missense
NM_001407907.1:c.4952C>T	NP_001394836.1:p.Ser1651Phe	missense
NM_001407908.1:c.4952C>T	NP_001394837.1:p.Ser1651Phe	missense
NM_001407909.1:c.4952C>T	NP_001394838.1:p.Ser1651Phe	missense
NM_001407910.1:c.4952C>T	NP_001394839.1:p.Ser1651Phe	missense
NM_001407915.1:c.4949C>T	NP_001394844.1:p.Ser1650Phe	missense
NM_001407916.1:c.4949C>T	NP_001394845.1:p.Ser1650Phe	missense
NM_001407917.1:c.4949C>T	NP_001394846.1:p.Ser1650Phe	missense
NM_001407918.1:c.4949C>T	NP_001394847.1:p.Ser1650Phe	missense
NM_001407919.1:c.5042C>T	NP_001394848.1:p.Ser1681Phe	missense
NM_001407920.1:c.4901C>T	NP_001394849.1:p.Ser1634Phe	missense
NM_001407921.1:c.4901C>T	NP_001394850.1:p.Ser1634Phe	missense
NM_001407922.1:c.4901C>T	NP_001394851.1:p.Ser1634Phe	missense
NM_001407923.1:c.4901C>T	NP_001394852.1:p.Ser1634Phe	missense
NM_001407924.1:c.4901C>T	NP_001394853.1:p.Ser1634Phe	missense
NM_001407925.1:c.4901C>T	NP_001394854.1:p.Ser1634Phe	missense
NM_001407926.1:c.4901C>T	NP_001394855.1:p.Ser1634Phe	missense
NM_001407927.1:c.4898C>T	NP_001394856.1:p.Ser1633Phe	missense
NM_001407928.1:c.4898C>T	NP_001394857.1:p.Ser1633Phe	missense
NM_001407929.1:c.4898C>T	NP_001394858.1:p.Ser1633Phe	missense
NM_001407930.1:c.4898C>T	NP_001394859.1:p.Ser1633Phe	missense
NM_001407931.1:c.4898C>T	NP_001394860.1:p.Ser1633Phe	missense
NM_001407932.1:c.4898C>T	NP_001394861.1:p.Ser1633Phe	missense
NM_001407933.1:c.4898C>T	NP_001394862.1:p.Ser1633Phe	missense
NM_001407934.1:c.4895C>T	NP_001394863.1:p.Ser1632Phe	missense
NM_001407935.1:c.4895C>T	NP_001394864.1:p.Ser1632Phe	missense
NM_001407936.1:c.4895C>T	NP_001394865.1:p.Ser1632Phe	missense
NM_001407937.1:c.5042C>T	NP_001394866.1:p.Ser1681Phe	missense
NM_001407938.1:c.5042C>T	NP_001394867.1:p.Ser1681Phe	missense
NM_001407939.1:c.5039C>T	NP_001394868.1:p.Ser1680Phe	missense
NM_001407940.1:c.5039C>T	NP_001394869.1:p.Ser1680Phe	missense
NM_001407941.1:c.5036C>T	NP_001394870.1:p.Ser1679Phe	missense
NM_001407942.1:c.5024C>T	NP_001394871.1:p.Ser1675Phe	missense
NM_001407943.1:c.5021C>T	NP_001394872.1:p.Ser1674Phe	missense
NM_001407944.1:c.5021C>T	NP_001394873.1:p.Ser1674Phe	missense
NM_001407945.1:c.5021C>T	NP_001394874.1:p.Ser1674Phe	missense
NM_001407946.1:c.4832C>T	NP_001394875.1:p.Ser1611Phe	missense
NM_001407947.1:c.4832C>T	NP_001394876.1:p.Ser1611Phe	missense
NM_001407948.1:c.4832C>T	NP_001394877.1:p.Ser1611Phe	missense
NM_001407949.1:c.4832C>T	NP_001394878.1:p.Ser1611Phe	missense
NM_001407950.1:c.4829C>T	NP_001394879.1:p.Ser1610Phe	missense
NM_001407951.1:c.4829C>T	NP_001394880.1:p.Ser1610Phe	missense
NM_001407952.1:c.4829C>T	NP_001394881.1:p.Ser1610Phe	missense
NM_001407953.1:c.4829C>T	NP_001394882.1:p.Ser1610Phe	missense
NM_001407954.1:c.4829C>T	NP_001394883.1:p.Ser1610Phe	missense
NM_001407955.1:c.4829C>T	NP_001394884.1:p.Ser1610Phe	missense
NM_001407956.1:c.4826C>T	NP_001394885.1:p.Ser1609Phe	missense
NM_001407957.1:c.4826C>T	NP_001394886.1:p.Ser1609Phe	missense
NM_001407958.1:c.4826C>T	NP_001394887.1:p.Ser1609Phe	missense
NM_001407959.1:c.4784C>T	NP_001394888.1:p.Ser1595Phe	missense
NM_001407960.1:c.4781C>T	NP_001394889.1:p.Ser1594Phe	missense
NM_001407962.1:c.4781C>T	NP_001394891.1:p.Ser1594Phe	missense
NM_001407963.1:c.4778C>T	NP_001394892.1:p.Ser1593Phe	missense
NM_001407964.1:c.4703C>T	NP_001394893.1:p.Ser1568Phe	missense
NM_001407965.1:c.4658C>T	NP_001394894.1:p.Ser1553Phe	missense
NM_001407966.1:c.4277C>T	NP_001394895.1:p.Ser1426Phe	missense
NM_001407967.1:c.4274C>T	NP_001394896.1:p.Ser1425Phe	missense
NM_001407968.1:c.2561C>T	NP_001394897.1:p.Ser854Phe	missense
NM_001407969.1:c.2558C>T	NP_001394898.1:p.Ser853Phe	missense
NM_001407970.1:c.1922C>T	NP_001394899.1:p.Ser641Phe	missense
NM_001407971.1:c.1922C>T	NP_001394900.1:p.Ser641Phe	missense
NM_001407972.1:c.1919C>T	NP_001394901.1:p.Ser640Phe	missense
NM_001407973.1:c.1856C>T	NP_001394902.1:p.Ser619Phe	missense
NM_001407974.1:c.1856C>T	NP_001394903.1:p.Ser619Phe	missense
NM_001407975.1:c.1856C>T	NP_001394904.1:p.Ser619Phe	missense
NM_001407976.1:c.1856C>T	NP_001394905.1:p.Ser619Phe	missense
NM_001407977.1:c.1856C>T	NP_001394906.1:p.Ser619Phe	missense
NM_001407978.1:c.1856C>T	NP_001394907.1:p.Ser619Phe	missense
NM_001407979.1:c.1853C>T	NP_001394908.1:p.Ser618Phe	missense
NM_001407980.1:c.1853C>T	NP_001394909.1:p.Ser618Phe	missense
NM_001407981.1:c.1853C>T	NP_001394910.1:p.Ser618Phe	missense
NM_001407982.1:c.1853C>T	NP_001394911.1:p.Ser618Phe	missense
NM_001407983.1:c.1853C>T	NP_001394912.1:p.Ser618Phe	missense
NM_001407984.1:c.1853C>T	NP_001394913.1:p.Ser618Phe	missense
NM_001407985.1:c.1853C>T	NP_001394914.1:p.Ser618Phe	missense
NM_001407986.1:c.1853C>T	NP_001394915.1:p.Ser618Phe	missense
NM_001407990.1:c.1853C>T	NP_001394919.1:p.Ser618Phe	missense
NM_001407991.1:c.1853C>T	NP_001394920.1:p.Ser618Phe	missense
NM_001407992.1:c.1853C>T	NP_001394921.1:p.Ser618Phe	missense
NM_001407993.1:c.1853C>T	NP_001394922.1:p.Ser618Phe	missense
NM_001408392.1:c.1850C>T	NP_001395321.1:p.Ser617Phe	missense
NM_001408396.1:c.1850C>T	NP_001395325.1:p.Ser617Phe	missense
NM_001408397.1:c.1850C>T	NP_001395326.1:p.Ser617Phe	missense
NM_001408398.1:c.1850C>T	NP_001395327.1:p.Ser617Phe	missense
NM_001408399.1:c.1850C>T	NP_001395328.1:p.Ser617Phe	missense
NM_001408400.1:c.1850C>T	NP_001395329.1:p.Ser617Phe	missense
NM_001408401.1:c.1850C>T	NP_001395330.1:p.Ser617Phe	missense
NM_001408402.1:c.1850C>T	NP_001395331.1:p.Ser617Phe	missense
NM_001408403.1:c.1850C>T	NP_001395332.1:p.Ser617Phe	missense
NM_001408404.1:c.1850C>T	NP_001395333.1:p.Ser617Phe	missense
NM_001408406.1:c.1847C>T	NP_001395335.1:p.Ser616Phe	missense
NM_001408407.1:c.1847C>T	NP_001395336.1:p.Ser616Phe	missense
NM_001408408.1:c.1847C>T	NP_001395337.1:p.Ser616Phe	missense
NM_001408409.1:c.1844C>T	NP_001395338.1:p.Ser615Phe	missense
NM_001408410.1:c.1781C>T	NP_001395339.1:p.Ser594Phe	missense
NM_001408411.1:c.1778C>T	NP_001395340.1:p.Ser593Phe	missense
NM_001408412.1:c.1775C>T	NP_001395341.1:p.Ser592Phe	missense
NM_001408413.1:c.1775C>T	NP_001395342.1:p.Ser592Phe	missense
NM_001408414.1:c.1775C>T	NP_001395343.1:p.Ser592Phe	missense
NM_001408415.1:c.1775C>T	NP_001395344.1:p.Ser592Phe	missense
NM_001408416.1:c.1775C>T	NP_001395345.1:p.Ser592Phe	missense
NM_001408418.1:c.1739C>T	NP_001395347.1:p.Ser580Phe	missense
NM_001408419.1:c.1739C>T	NP_001395348.1:p.Ser580Phe	missense
NM_001408420.1:c.1739C>T	NP_001395349.1:p.Ser580Phe	missense
NM_001408421.1:c.1736C>T	NP_001395350.1:p.Ser579Phe	missense
NM_001408422.1:c.1736C>T	NP_001395351.1:p.Ser579Phe	missense
NM_001408423.1:c.1736C>T	NP_001395352.1:p.Ser579Phe	missense
NM_001408424.1:c.1736C>T	NP_001395353.1:p.Ser579Phe	missense
NM_001408425.1:c.1733C>T	NP_001395354.1:p.Ser578Phe	missense
NM_001408426.1:c.1733C>T	NP_001395355.1:p.Ser578Phe	missense
NM_001408427.1:c.1733C>T	NP_001395356.1:p.Ser578Phe	missense
NM_001408428.1:c.1733C>T	NP_001395357.1:p.Ser578Phe	missense
NM_001408429.1:c.1733C>T	NP_001395358.1:p.Ser578Phe	missense
NM_001408430.1:c.1733C>T	NP_001395359.1:p.Ser578Phe	missense
NM_001408431.1:c.1733C>T	NP_001395360.1:p.Ser578Phe	missense
NM_001408432.1:c.1730C>T	NP_001395361.1:p.Ser577Phe	missense
NM_001408433.1:c.1730C>T	NP_001395362.1:p.Ser577Phe	missense
NM_001408434.1:c.1730C>T	NP_001395363.1:p.Ser577Phe	missense
NM_001408435.1:c.1730C>T	NP_001395364.1:p.Ser577Phe	missense
NM_001408436.1:c.1730C>T	NP_001395365.1:p.Ser577Phe	missense
NM_001408437.1:c.1730C>T	NP_001395366.1:p.Ser577Phe	missense
NM_001408438.1:c.1730C>T	NP_001395367.1:p.Ser577Phe	missense
NM_001408439.1:c.1730C>T	NP_001395368.1:p.Ser577Phe	missense
NM_001408440.1:c.1730C>T	NP_001395369.1:p.Ser577Phe	missense
NM_001408441.1:c.1730C>T	NP_001395370.1:p.Ser577Phe	missense
NM_001408442.1:c.1730C>T	NP_001395371.1:p.Ser577Phe	missense
NM_001408443.1:c.1730C>T	NP_001395372.1:p.Ser577Phe	missense
NM_001408444.1:c.1730C>T	NP_001395373.1:p.Ser577Phe	missense
NM_001408445.1:c.1727C>T	NP_001395374.1:p.Ser576Phe	missense
NM_001408446.1:c.1727C>T	NP_001395375.1:p.Ser576Phe	missense
NM_001408447.1:c.1727C>T	NP_001395376.1:p.Ser576Phe	missense
NM_001408448.1:c.1727C>T	NP_001395377.1:p.Ser576Phe	missense
NM_001408450.1:c.1727C>T	NP_001395379.1:p.Ser576Phe	missense
NM_001408451.1:c.1721C>T	NP_001395380.1:p.Ser574Phe	missense
NM_001408452.1:c.1715C>T	NP_001395381.1:p.Ser572Phe	missense
NM_001408453.1:c.1715C>T	NP_001395382.1:p.Ser572Phe	missense
NM_001408454.1:c.1715C>T	NP_001395383.1:p.Ser572Phe	missense
NM_001408455.1:c.1715C>T	NP_001395384.1:p.Ser572Phe	missense
NM_001408456.1:c.1715C>T	NP_001395385.1:p.Ser572Phe	missense
NM_001408457.1:c.1715C>T	NP_001395386.1:p.Ser572Phe	missense
NM_001408458.1:c.1712C>T	NP_001395387.1:p.Ser571Phe	missense
NM_001408459.1:c.1712C>T	NP_001395388.1:p.Ser571Phe	missense
NM_001408460.1:c.1712C>T	NP_001395389.1:p.Ser571Phe	missense
NM_001408461.1:c.1712C>T	NP_001395390.1:p.Ser571Phe	missense
NM_001408462.1:c.1712C>T	NP_001395391.1:p.Ser571Phe	missense
NM_001408463.1:c.1712C>T	NP_001395392.1:p.Ser571Phe	missense
NM_001408464.1:c.1712C>T	NP_001395393.1:p.Ser571Phe	missense
NM_001408465.1:c.1712C>T	NP_001395394.1:p.Ser571Phe	missense
NM_001408466.1:c.1712C>T	NP_001395395.1:p.Ser571Phe	missense
NM_001408467.1:c.1712C>T	NP_001395396.1:p.Ser571Phe	missense
NM_001408468.1:c.1709C>T	NP_001395397.1:p.Ser570Phe	missense
NM_001408469.1:c.1709C>T	NP_001395398.1:p.Ser570Phe	missense
NM_001408470.1:c.1709C>T	NP_001395399.1:p.Ser570Phe	missense
NM_001408472.1:c.1853C>T	NP_001395401.1:p.Ser618Phe	missense
NM_001408473.1:c.1850C>T	NP_001395402.1:p.Ser617Phe	missense
NM_001408474.1:c.1655C>T	NP_001395403.1:p.Ser552Phe	missense
NM_001408475.1:c.1652C>T	NP_001395404.1:p.Ser551Phe	missense
NM_001408476.1:c.1652C>T	NP_001395405.1:p.Ser551Phe	missense
NM_001408478.1:c.1646C>T	NP_001395407.1:p.Ser549Phe	missense
NM_001408479.1:c.1646C>T	NP_001395408.1:p.Ser549Phe	missense
NM_001408480.1:c.1646C>T	NP_001395409.1:p.Ser549Phe	missense
NM_001408481.1:c.1643C>T	NP_001395410.1:p.Ser548Phe	missense
NM_001408482.1:c.1643C>T	NP_001395411.1:p.Ser548Phe	missense
NM_001408483.1:c.1643C>T	NP_001395412.1:p.Ser548Phe	missense
NM_001408484.1:c.1643C>T	NP_001395413.1:p.Ser548Phe	missense
NM_001408485.1:c.1643C>T	NP_001395414.1:p.Ser548Phe	missense
NM_001408489.1:c.1643C>T	NP_001395418.1:p.Ser548Phe	missense
NM_001408490.1:c.1643C>T	NP_001395419.1:p.Ser548Phe	missense
NM_001408491.1:c.1643C>T	NP_001395420.1:p.Ser548Phe	missense
NM_001408492.1:c.1640C>T	NP_001395421.1:p.Ser547Phe	missense
NM_001408493.1:c.1640C>T	NP_001395422.1:p.Ser547Phe	missense
NM_001408494.1:c.1616C>T	NP_001395423.1:p.Ser539Phe	missense
NM_001408495.1:c.1610C>T	NP_001395424.1:p.Ser537Phe	missense
NM_001408496.1:c.1592C>T	NP_001395425.1:p.Ser531Phe	missense
NM_001408497.1:c.1592C>T	NP_001395426.1:p.Ser531Phe	missense
NM_001408498.1:c.1592C>T	NP_001395427.1:p.Ser531Phe	missense
NM_001408499.1:c.1592C>T	NP_001395428.1:p.Ser531Phe	missense
NM_001408500.1:c.1592C>T	NP_001395429.1:p.Ser531Phe	missense
NM_001408501.1:c.1592C>T	NP_001395430.1:p.Ser531Phe	missense
NM_001408502.1:c.1589C>T	NP_001395431.1:p.Ser530Phe	missense
NM_001408503.1:c.1589C>T	NP_001395432.1:p.Ser530Phe	missense
NM_001408504.1:c.1589C>T	NP_001395433.1:p.Ser530Phe	missense
NM_001408505.1:c.1586C>T	NP_001395434.1:p.Ser529Phe	missense
NM_001408506.1:c.1529C>T	NP_001395435.1:p.Ser510Phe	missense
NM_001408507.1:c.1526C>T	NP_001395436.1:p.Ser509Phe	missense
NM_001408508.1:c.1517C>T	NP_001395437.1:p.Ser506Phe	missense
NM_001408509.1:c.1514C>T	NP_001395438.1:p.Ser505Phe	missense
NM_001408510.1:c.1475C>T	NP_001395439.1:p.Ser492Phe	missense
NM_001408511.1:c.1472C>T	NP_001395440.1:p.Ser491Phe	missense
NM_001408512.1:c.1352C>T	NP_001395441.1:p.Ser451Phe	missense
NM_001408513.1:c.1325C>T	NP_001395442.1:p.Ser442Phe	missense
NM_001408514.1:c.929C>T	NP_001395443.1:p.Ser310Phe	missense
NM_007297.4:c.5024C>T	NP_009228.2:p.Ser1675Phe	missense
NM_007298.4:c.1853C>T	NP_009229.2:p.Ser618Phe	missense
NM_007299.4:c.1853C>T	NP_009230.2:p.Ser618Phe	missense
NM_007300.4:c.5228C>T	NP_009231.2:p.Ser1743Phe	missense
NM_007304.2:c.1853C>T	NP_009235.2:p.Ser618Phe	missense
NR_027676.2:n.5342C>T		non-coding transcript variant
NC_000017.11:g.43063361G>A
NC_000017.10:g.41215378G>A
NG_005905.2:g.154623C>T
LRG_292:g.154623C>T
LRG_292t1:c.5165C>T	LRG_292p1:p.Ser1722Phe
U14680.1:n.5284C>T

... more HGVS ... less HGVS

Protein change

S1722F, S1675F, S1743F, S618F, S1674F, S1680F, S1702F, S1718F, S451F, S506F, S510F, S529F, S530F, S549F, S574F, S592F, S593F, S616F, S854F, S310F, S537F, S548F, S572F, S577F, S580F, S594F, S617F, S619F, S641F, S1593F, S1595F, S1634F, S1654F, S1553F, S1568F, S1609F, S1610F, S1632F, S1673F, S1681F, S1695F, S1703F, S1719F, S1720F, S1744F, S491F, S492F, S531F, S552F, S570F, S578F, S579F, S615F, S853F, S1425F, S1594F, S1611F, S1633F, S1651F, S1653F, S1655F, S1679F, S1694F, S442F, S505F, S509F, S539F, S547F, S551F, S571F, S576F, S640F, S1426F, S1650F, S1652F, S1678F, S1696F, S1717F, S1721F, S1742F

Other names

5284C>T

Canonical SPDI

NC_000017.11:43063360:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

function_uncertain_variant; Sequence Ontology [ SO:0002220]

The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5165C>T, a MISSENSE variant, produced a function score of -0.83, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA003318 dbSNP: rs80357104 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRCA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	13050	14856

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Hereditary breast ovarian cancer syndrome	Pathogenic/Likely pathogenic (4)	criteria provided, multiple submitters, no conflicts	Jan 28, 2024	RCV000048839.23
Breast-ovarian cancer, familial, susceptibility to, 1	Pathogenic/Likely pathogenic (9)	criteria provided, multiple submitters, no conflicts	Mar 27, 2024	RCV000077606.18
Hereditary cancer-predisposing syndrome	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Nov 8, 2022	RCV000214443.15
not provided	Pathogenic/Likely pathogenic (3)	criteria provided, multiple submitters, no conflicts	Aug 15, 2023	RCV000236284.16
Malignant tumor of breast	Likely pathogenic (1)	no assertion criteria provided	-	RCV001354040.4
Breast-ovarian cancer, familial, susceptibility to, 1 Familial cancer of breast Fanconi anemia, complementation group S Pancreatic cancer, susceptibility to, 4	Likely pathogenic (1)	criteria provided, single submitter	Jul 14, 2021	RCV002490620.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001140481.1 First in ClinVar: Jan 10, 2020 Last updated: Jan 10, 2020
Likely pathogenic (May 11, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000699216.2 First in ClinVar: Aug 27, 2017 Last updated: May 21, 2021	Publications: PubMed (21) PubMed: 16267036‚ 15385441‚ 15172985‚ 20516115‚ 17305420‚ 20378548‚ 12496477‚ 22476429‚ 23704879‚ 25085752‚ 24845084‚ 29446198‚ 30093976‚ 30209399‚ 28781887‚ 30765603‚ 31481248‚ 30264118‚ 33206196‚ 33010199‚ 30875412 Comment: Variant summary: BRCA1 c.5165C>T (p.Ser1722Phe) results in a non-conservative amino acid change located in the first BRCT domain (IPR001357) that binds ATM-phosphorylated proteins (e.g. abraxas, … (more) Variant summary: BRCA1 c.5165C>T (p.Ser1722Phe) results in a non-conservative amino acid change located in the first BRCT domain (IPR001357) that binds ATM-phosphorylated proteins (e.g. abraxas, CtIP and BRIP1; see PMID 22193408). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251036 control chromosomes (gnomAD). c.5165C>T has been reported in the literature in individuals with personal and/or family history of breast- and ovarian cancer (Judkins_2005, Lu_2012, Chan_2018, Lynce_2020). Publications also reported experimental evidence, demonstrating decreased structural stability, impaired phosphopeptide binding and transcriptional activity (Lee_2010); and in a recent high throughput genome editing assay the variant resulted in a decreased (intermediate) function when testing it in a haploid human cell line whose survival is dependent on intact BRCA1 function (Findlay_2018). Ten other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2) or likely pathogenic (n=8). Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
Pathogenic (Oct 02, 2015)	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: germline	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge Accession: SCV000326192.4 First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022
Likely pathogenic (Apr 19, 2017)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000677659.2 First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022	Publications: PubMed (6) PubMed: 17305420‚ 15172985‚ 22476429‚ 20516115‚ 12496477‚ 25085752
Likely pathogenic (May 04, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000293277.13 First in ClinVar: Jul 24, 2016 Last updated: May 20, 2023	Comment: Published functional studies demonstrate a damaging effect with respect to protein folding, phosphopeptide binding activity and specificity, transcriptional activity, homology-directed repair, and cell viability (Carvhalo … (more) Published functional studies demonstrate a damaging effect with respect to protein folding, phosphopeptide binding activity and specificity, transcriptional activity, homology-directed repair, and cell viability (Carvhalo et al., 2002; Lee et al., 2010; Findlay et al., 2018; Fernandes et al., 2019; Iversen et al., 2022); Observed in individuals with BRCA1-related cancers (Lu et al., 2012; Chan et al., 2018; Mersch et al., 2018; Ow et al., 2019; Guindalini et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5284C>T; This variant is associated with the following publications: (PMID: 15172985, 30209399, 16267036, 20516115, 25085752, 12496477, 17305420, 22476429, 28781887, 15385441, 29446198, 23704879, 30264118, 30093976, 30765603, 31447099, 33087888, 30875412, 30787465, 33526602, 25348405, 32377563, 35665744, 29884841, 35264596, 33206196, 33010199) (less)
Likely pathogenic (Aug 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002550949.4 First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023
Pathogenic (Nov 08, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000683267.6 First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024	Publications: PubMed (7) PubMed: 12496477‚ 15172985‚ 20516115‚ 22476429‚ 25085752‚ 30765603‚ 33526602 Comment: This missense variant replaces serine with phenylalanine at codon 1722 in the BRCT1 domain of the BRCA1 protein. Computational prediction suggests that this variant may … (more) This missense variant replaces serine with phenylalanine at codon 1722 in the BRCT1 domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Multiple functional studies have consistently shown that this variant results in the loss of transcription activation function of BRCA1 protein (PMID: 12496477, 15172985, 20516115, 30765603). This variant has been reported in at least six individuals affected with hereditary breast and/or ovarian cancer (PMID: 22476429, 33526602; Color internal data). An external laboratory has concluded this variant to be Pathogenic based on analysis of personal and family history of 44 probands (PMID: 25085752). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less)
Likely pathogenic (Jan 28, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000076852.13 First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024	Publications: PubMed (6) PubMed: 22476429‚ 28888541‚ 30093976‚ 35264596‚ 12496477‚ 20516115 Comment: This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1722 of the BRCA1 protein (p.Ser1722Phe). … (more) This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1722 of the BRCA1 protein (p.Ser1722Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 22476429, 28888541, 30093976, 35264596). ClinVar contains an entry for this variant (Variation ID: 55441). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 12496477, 20516115). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
Likely Pathogenic (Jan 23, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847823.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Publications: PubMed (10) PubMed: 22476429‚ 26295337‚ 15172985‚ 23704879‚ 20516115‚ 15385441‚ 25085752‚ 12496477‚ 16267036‚ 17305420 Comment: The p.Ser1722Phe variant in BRCA1 has been reported in at least 3 individual with breast cancer (Lu 2012, Breast Information Core (BIC) database). In addition, … (more) The p.Ser1722Phe variant in BRCA1 has been reported in at least 3 individual with breast cancer (Lu 2012, Breast Information Core (BIC) database). In addition, this variant has also been reported in ClinVar (Variation ID 55441) and was absent from large population databases. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies support an impact on protein function (Lee 2010, Carvalho 2002 ). In addition, this variant lies within a binding motif in BRCA1. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Hereditary breast and ovarian cancer. PM1, PM2, PP3, PS3_Supporting, PS4_Supporting (less)
Likely pathogenic (Mar 27, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004215091.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Likely pathogenic (May 25, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: germline	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine Accession: SCV000839899.1 First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016	Comment: The c.5165C>T (p.Ser1722Phe) variant in the BRCA1 gene has been reported in two patients in the Breast Cancer Information Core database (accession number 10462 and … (more) The c.5165C>T (p.Ser1722Phe) variant in the BRCA1 gene has been reported in two patients in the Breast Cancer Information Core database (accession number 10462 and 10461). The variant has also been reported in additional patients by clinical laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/55441). Functional assays showed a strong deleterious effect [PMID 20516115]. This variant was not observed in the ExAC database. Serine at amino acid position 1722 of the BRCA1 protein is conserved in mammals. Although not validated for clinical use, computer-based algorithms SIFT and Polyphen2 predict this p.Ser1722Phe change to be deleterious. This variant thus classified as likely pathogenic. (less)
Likely pathogenic (Jul 14, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast Breast-ovarian cancer, familial, susceptibility to, 1 Pancreatic cancer, susceptibility to, 4 Fanconi anemia, complementation group S Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002787757.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Pathogenic (Mar 29, 2021)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000296373.7 First in ClinVar: May 27, 2015 Last updated: Jan 06, 2024	Publications: PubMed (11) PubMed: 26295337‚ 33010199‚ 17305420‚ 20516115‚ 15172985‚ 16267036‚ 12496477‚ 30093976‚ 31481248‚ 29446198‚ 28781887 Comment: This variant has been reported in individuals and families affected with breast/ovarian cancer (PMID: 16267036 (2005), 22476429 (2012), 29446198 (2018), 30093976 (2018), 30264118 (2018), 31481248 … (more) This variant has been reported in individuals and families affected with breast/ovarian cancer (PMID: 16267036 (2005), 22476429 (2012), 29446198 (2018), 30093976 (2018), 30264118 (2018), 31481248 (2019), 33010199 (2020)) and described as pathogenic based on a multifactorial likelihood algorithm in the published literature (PMID: 25085752 (2014)). In addition, functional studies describe the p.Ser1722Phe variant as having a deleterious effect on BRCA1 protein function (PMID: 12496477 (2002), 15172985 (2004), 20516115 (2010)). Based on the available information, this variant is classified as pathogenic. (less)
Pathogenic (Apr 10, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004817580.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Publications: PubMed (7) PubMed: 12496477‚ 15172985‚ 20516115‚ 22476429‚ 25085752‚ 30765603‚ 33526602 Comment: This missense variant replaces serine with phenylalanine at codon 1722 in the BRCT1 domain of the BRCA1 protein. Computational prediction suggests that this variant may … (more) This missense variant replaces serine with phenylalanine at codon 1722 in the BRCT1 domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Multiple functional studies have consistently shown that this variant results in the loss of transcription activation function of BRCA1 protein (PMID: 12496477, 15172985, 20516115, 30765603). This variant has been reported in at least six individuals affected with hereditary breast and/or ovarian cancer (PMID: 22476429, 33526602; Color internal data). An external laboratory has concluded this variant to be Pathogenic based on analysis of personal and family history of 44 probands (PMID: 25085752). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. (less) Number of individuals with the variant: 1
Pathogenic (Aug 27, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000273727.7 First in ClinVar: May 29, 2016 Last updated: May 01, 2024	Publications: PubMed (7) PubMed: 16267036‚ 23704879‚ 28781887‚ 29446198‚ 30093976‚ 30209399‚ 31447099 Comment: The p.S1722F pathogenic mutation (also known as c.5165C>T), located in coding exon 17 of the BRCA1 gene, results from a C to T substitution at … (more) The p.S1722F pathogenic mutation (also known as c.5165C>T), located in coding exon 17 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5165. The serine at codon 1722 is replaced by phenylalanine, an amino acid with highly dissimilar properties. Based on multiple structural and functional analyses, this alteration was shown to significantly alter protease sensitivity, peptide binding activity, peptide binding specificity, and transcriptional activity of the mutant protein compared to wild type (Mirkovic N et al. Cancer Res. 2004 Jun;64:3790-7; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Pathogenic (May 12, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	hereditary breast and ovarian cancer syndrome Affected status: unknown Allele origin: unknown	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine Accession: SCV005045702.1 First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024	Comment: The c.5165C>T (p.Ser1722Phe) variant in the BRCA1 gene has been reported in two patients in the Breast Cancer Information Core database (accession number 10462 and … (more) The c.5165C>T (p.Ser1722Phe) variant in the BRCA1 gene has been reported in two patients in the Breast Cancer Information Core database (accession number 10462 and 10461). The variant has also been reported in additional patients by clinical laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/55441). Functional assays showed a strong deleterious effect [PMID 20516115]. This variant was not observed in the ExAC database. Serine at amino acid position 1722 of the BRCA1 protein is conserved in mammals. Although not validated for clinical use, computer-based algorithms SIFT and Polyphen2 predict this p.Ser1722Phe change to be deleterious. This variant thus classified as likely pathogenic. (less)
Uncertain significance (Feb 20, 2004)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 1 Affected status: yes Allele origin: germline	Breast Cancer Information Core (BIC) (BRCA1) Accession: SCV000145368.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014	Number of individuals with the variant: 2 Ethnicity/Population group: Latin American, Caribbean
Pathogenic (Aug 17, 2012)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 1 Affected status: not provided Allele origin: germline	Sharing Clinical Reports Project (SCRP) Accession: SCV000109409.2 First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	Malignant tumor of breast Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV000591589.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021	Comment: The BRCA1 p.Ser1722Ph variant falls within the BRCA1 C-terminus (BRCT) domain and was shown, in a yeast based transcription activation assay, to be temperature sensitive … (more) The BRCA1 p.Ser1722Ph variant falls within the BRCA1 C-terminus (BRCT) domain and was shown, in a yeast based transcription activation assay, to be temperature sensitive whereby activity was abolished at 37oC, and therefore likely represents a cancer-associated variant (Carvalho 2002). Lee et al (2010) used 3 biochemical and cell-based transcriptional assays to show that the variant had a strong functional effect and is likely associated with increased cancer risk. Other functional/computational models validated by such biochemical assays have also shown the variant to be deleterious (Mirkovic 2004, Karchin 2007). The variant was also identified in dbSNP (ID: rs80357104) â€šÃ„ÃºWith other alleleâ€šÃ„Ã¹, but no frequency information was provided, the variant was not identified in NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) or the 1000 Genomes Browser. The variant was present in the Clinvitae database, the ClinVar database (with conflicting interpretations of pathogenicity: classified as pathogenic by Sharing Clinical Reports Project derived from Myriad reports; uncertain significance by BIC, and classification not provided by Invitae), Fanconi Anemia Mutation Database (LOVD), COSMIC (1x in a cervical tissue/squamous cell carcinoma), the BIC database (2X with unknown clinical importance), and UMD (1X with a 3-UV â€šÃ„Ã¹unclassified variantâ€šÃ„Ã¹). The p.Ser1722 residue is conserved across mammals and most other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Phe variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as likely pathogenic. (less)
not provided (-)	no classification provided Method: in vitro	Breast-ovarian cancer, familial 1 Affected status: not applicable Allele origin: not applicable	Brotman Baty Institute, University of Washington Accession: SCV001237797.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020	Publications: PubMed (1) PubMed: 30209399 Other databases https://sge.gs.washington.edu/BR… https://sge.gs.washington.edu/BRCA1/ Method: saturation genome editing in haploid cells Result: INTERMEDIATE:-0.834246378904467
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Comment:

Variant summary: BRCA1 c.5165C>T (p.Ser1722Phe) results in a non-conservative amino acid change located in the first BRCT domain (IPR001357) that binds ATM-phosphorylated proteins (e.g. abraxas, CtIP and BRIP1; see PMID 22193408). Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251036 control chromosomes (gnomAD). c.5165C>T has been reported in the literature in individuals with personal and/or family history of breast- and ovarian cancer (Judkins_2005, Lu_2012, Chan_2018, Lynce_2020). Publications also reported experimental evidence, demonstrating decreased structural stability, impaired phosphopeptide binding and transcriptional activity (Lee_2010); and in a recent high throughput genome editing assay the variant resulted in a decreased (intermediate) function when testing it in a haploid human cell line whose survival is dependent on intact BRCA1 function (Findlay_2018). Ten other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=2) or likely pathogenic (n=8). Based on the evidence outlined above, the variant was classified as likely pathogenic.

Comment:

Published functional studies demonstrate a damaging effect with respect to protein folding, phosphopeptide binding activity and specificity, transcriptional activity, homology-directed repair, and cell viability (Carvhalo et al., 2002; Lee et al., 2010; Findlay et al., 2018; Fernandes et al., 2019; Iversen et al., 2022); Observed in individuals with BRCA1-related cancers (Lu et al., 2012; Chan et al., 2018; Mersch et al., 2018; Ow et al., 2019; Guindalini et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 5284C>T; This variant is associated with the following publications: (PMID: 15172985, 30209399, 16267036, 20516115, 25085752, 12496477, 17305420, 22476429, 28781887, 15385441, 29446198, 23704879, 30264118, 30093976, 30765603, 31447099, 33087888, 30875412, 30787465, 33526602, 25348405, 32377563, 35665744, 29884841, 35264596, 33206196, 33010199)

Comment:

This missense variant replaces serine with phenylalanine at codon 1722 in the BRCT1 domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Multiple functional studies have consistently shown that this variant results in the loss of transcription activation function of BRCA1 protein (PMID: 12496477, 15172985, 20516115, 30765603). This variant has been reported in at least six individuals affected with hereditary breast and/or ovarian cancer (PMID: 22476429, 33526602; Color internal data). An external laboratory has concluded this variant to be Pathogenic based on analysis of personal and family history of 44 probands (PMID: 25085752). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

Comment:

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1722 of the BRCA1 protein (p.Ser1722Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 22476429, 28888541, 30093976, 35264596). ClinVar contains an entry for this variant (Variation ID: 55441). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRCA1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 12496477, 20516115). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

Comment:

The p.Ser1722Phe variant in BRCA1 has been reported in at least 3 individual with breast cancer (Lu 2012, Breast Information Core (BIC) database). In addition, this variant has also been reported in ClinVar (Variation ID 55441) and was absent from large population databases. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies support an impact on protein function (Lee 2010, Carvalho 2002 ). In addition, this variant lies within a binding motif in BRCA1. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Hereditary breast and ovarian cancer. PM1, PM2, PP3, PS3_Supporting, PS4_Supporting

Comment:

The c.5165C>T (p.Ser1722Phe) variant in the BRCA1 gene has been reported in two patients in the Breast Cancer Information Core database (accession number 10462 and 10461). The variant has also been reported in additional patients by clinical laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/55441). Functional assays showed a strong deleterious effect [PMID 20516115]. This variant was not observed in the ExAC database. Serine at amino acid position 1722 of the BRCA1 protein is conserved in mammals. Although not validated for clinical use, computer-based algorithms SIFT and Polyphen2 predict this p.Ser1722Phe change to be deleterious. This variant thus classified as likely pathogenic.

Comment:

This variant has been reported in individuals and families affected with breast/ovarian cancer (PMID: 16267036 (2005), 22476429 (2012), 29446198 (2018), 30093976 (2018), 30264118 (2018), 31481248 (2019), 33010199 (2020)) and described as pathogenic based on a multifactorial likelihood algorithm in the published literature (PMID: 25085752 (2014)). In addition, functional studies describe the p.Ser1722Phe variant as having a deleterious effect on BRCA1 protein function (PMID: 12496477 (2002), 15172985 (2004), 20516115 (2010)). Based on the available information, this variant is classified as pathogenic.

Comment:

The p.S1722F pathogenic mutation (also known as c.5165C>T), located in coding exon 17 of the BRCA1 gene, results from a C to T substitution at nucleotide position 5165. The serine at codon 1722 is replaced by phenylalanine, an amino acid with highly dissimilar properties. Based on multiple structural and functional analyses, this alteration was shown to significantly alter protease sensitivity, peptide binding activity, peptide binding specificity, and transcriptional activity of the mutant protein compared to wild type (Mirkovic N et al. Cancer Res. 2004 Jun;64:3790-7; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

Comment:

The BRCA1 p.Ser1722Ph variant falls within the BRCA1 C-terminus (BRCT) domain and was shown, in a yeast based transcription activation assay, to be temperature sensitive whereby activity was abolished at 37oC, and therefore likely represents a cancer-associated variant (Carvalho 2002). Lee et al (2010) used 3 biochemical and cell-based transcriptional assays to show that the variant had a strong functional effect and is likely associated with increased cancer risk. Other functional/computational models validated by such biochemical assays have also shown the variant to be deleterious (Mirkovic 2004, Karchin 2007). The variant was also identified in dbSNP (ID: rs80357104) â€šÃ„ÃºWith other alleleâ€šÃ„Ã¹, but no frequency information was provided, the variant was not identified in NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) or the 1000 Genomes Browser. The variant was present in the Clinvitae database, the ClinVar database (with conflicting interpretations of pathogenicity: classified as pathogenic by Sharing Clinical Reports Project derived from Myriad reports; uncertain significance by BIC, and classification not provided by Invitae), Fanconi Anemia Mutation Database (LOVD), COSMIC (1x in a cervical tissue/squamous cell carcinoma), the BIC database (2X with unknown clinical importance), and UMD (1X with a 3-UV â€šÃ„Ã¹unclassified variantâ€šÃ„Ã¹). The p.Ser1722 residue is conserved across mammals and most other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the Phe variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as likely pathogenic.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
function_uncertain_variant (SO:0002220)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	INTERMEDIATE:-0.834246378904467	Brotman Baty Institute, University of Washington Accession: SCV001237797.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5165C>T, a MISSENSE variant, produced a function score of -0.83, corresponding to a functional classification of INTERMEDIATE. … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5165C>T, a MISSENSE variant, produced a function score of -0.83, corresponding to a functional classification of INTERMEDIATE. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.	Guindalini RSC	Scientific reports	2022	PMID: 35264596
Oncologist-led BRCA counselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes.	Yoon SY	Journal of medical genetics	2022	PMID: 33526602
Cancer Previvors in an Active Duty Service Women Population: An Opportunity for Prevention and Increased Force Readiness.	Lovejoy LA	Military medicine	2021	PMID: 33206196
BRCA1/2 mutations and risk-reducing bilateral salpingo-oophorectomy among Latinas: The UPTAKE study.	Lynce F	Journal of genetic counseling	2021	PMID: 33010199
Using next-generation sequencing (NGS) platform to diagnose pathogenic germline BRCA1/2 mutations from archival tumor specimens.	Ong PY	Gynecologic oncology	2019	PMID: 31481248
Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network.	eMERGE Consortium. Electronic address: [email protected]	American journal of human genetics	2019	PMID: 31447099
Discoveries beyond BRCA1/2: Multigene testing in an Asian multi-ethnic cohort suspected of hereditary breast cancer syndrome in the real world.	Ow SGW	PloS one	2019	PMID: 30875412
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation.	Fernandes VC	The Journal of biological chemistry	2019	PMID: 30765603
Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing.	Mersch J	JAMA	2018	PMID: 30264118
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.	Chan GHJ	Oncotarget	2018	PMID: 30093976
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.	Rebbeck TR	Human mutation	2018	PMID: 29446198
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls.	Lilyquist J	Gynecologic oncology	2017	PMID: 28888541
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance.	Woods NT	NPJ genomic medicine	2016	PMID: 28781887
Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory.	Strom CM	PloS one	2015	PMID: 26295337
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.	Pruss D	Breast cancer research and treatment	2014	PMID: 25085752
Probing structure-function relationships in missense variants in the carboxy-terminal region of BRCA1.	Carvalho RS	PloS one	2014	PMID: 24845084
Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2.	Tram E	PloS one	2013	PMID: 23704879
Mutation screening of RAD51C in high-risk breast and ovarian cancer families.	Lu W	Familial cancer	2012	PMID: 22476429
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.	Lee MS	Cancer research	2010	PMID: 20516115
Toward classification of BRCA1 missense variants using a biophysical approach.	Rowling PJ	The Journal of biological chemistry	2010	PMID: 20378548
Functional impact of missense variants in BRCA1 predicted by supervised learning.	Karchin R	PLoS computational biology	2007	PMID: 17305420
Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations.	Judkins T	Cancer research	2005	PMID: 16267036
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.	Pavlicek A	Human molecular genetics	2004	PMID: 15385441
Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition.	Mirkovic N	Cancer research	2004	PMID: 15172985
Mutations in the BRCT domain confer temperature sensitivity to BRCA1 in transcription activation.	Carvalho MA	Cancer biology & therapy	2002	PMID: 12496477
https://sge.gs.washington.edu/BRCA1/	-	-	-	-
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Text-mined citations for rs80357104 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.5165C>T (p.Ser1722Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80357104 ...