VCV000230862.27 - ClinVar

NM_007294.4(BRCA1):c.122A>T (p.His41Leu)

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.

(10)

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.122A>T (p.His41Leu)

Variation ID: 230862 Accession: VCV000230862.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43115738 (GRCh38) [ NCBI UCSC ] 17: 41267755 (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	Aug 1, 2016	Sep 29, 2024	Aug 25, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.122A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.His41Leu	missense
NM_001407571.1:c.-67A>T
NM_001407581.1:c.122A>T	NP_001394510.1:p.His41Leu	missense
NM_001407582.1:c.122A>T	NP_001394511.1:p.His41Leu	missense
NM_001407583.1:c.122A>T	NP_001394512.1:p.His41Leu	missense
NM_001407585.1:c.122A>T	NP_001394514.1:p.His41Leu	missense
NM_001407587.1:c.122A>T	NP_001394516.1:p.His41Leu	missense
NM_001407590.1:c.122A>T	NP_001394519.1:p.His41Leu	missense
NM_001407591.1:c.122A>T	NP_001394520.1:p.His41Leu	missense
NM_001407593.1:c.122A>T	NP_001394522.1:p.His41Leu	missense
NM_001407594.1:c.122A>T	NP_001394523.1:p.His41Leu	missense
NM_001407596.1:c.122A>T	NP_001394525.1:p.His41Leu	missense
NM_001407597.1:c.122A>T	NP_001394526.1:p.His41Leu	missense
NM_001407598.1:c.122A>T	NP_001394527.1:p.His41Leu	missense
NM_001407602.1:c.122A>T	NP_001394531.1:p.His41Leu	missense
NM_001407603.1:c.122A>T	NP_001394532.1:p.His41Leu	missense
NM_001407605.1:c.122A>T	NP_001394534.1:p.His41Leu	missense
NM_001407610.1:c.122A>T	NP_001394539.1:p.His41Leu	missense
NM_001407611.1:c.122A>T	NP_001394540.1:p.His41Leu	missense
NM_001407612.1:c.122A>T	NP_001394541.1:p.His41Leu	missense
NM_001407613.1:c.122A>T	NP_001394542.1:p.His41Leu	missense
NM_001407614.1:c.122A>T	NP_001394543.1:p.His41Leu	missense
NM_001407615.1:c.122A>T	NP_001394544.1:p.His41Leu	missense
NM_001407616.1:c.122A>T	NP_001394545.1:p.His41Leu	missense
NM_001407617.1:c.122A>T	NP_001394546.1:p.His41Leu	missense
NM_001407618.1:c.122A>T	NP_001394547.1:p.His41Leu	missense
NM_001407619.1:c.122A>T	NP_001394548.1:p.His41Leu	missense
NM_001407620.1:c.122A>T	NP_001394549.1:p.His41Leu	missense
NM_001407621.1:c.122A>T	NP_001394550.1:p.His41Leu	missense
NM_001407622.1:c.122A>T	NP_001394551.1:p.His41Leu	missense
NM_001407623.1:c.122A>T	NP_001394552.1:p.His41Leu	missense
NM_001407624.1:c.122A>T	NP_001394553.1:p.His41Leu	missense
NM_001407625.1:c.122A>T	NP_001394554.1:p.His41Leu	missense
NM_001407626.1:c.122A>T	NP_001394555.1:p.His41Leu	missense
NM_001407627.1:c.122A>T	NP_001394556.1:p.His41Leu	missense
NM_001407628.1:c.122A>T	NP_001394557.1:p.His41Leu	missense
NM_001407629.1:c.122A>T	NP_001394558.1:p.His41Leu	missense
NM_001407630.1:c.122A>T	NP_001394559.1:p.His41Leu	missense
NM_001407631.1:c.122A>T	NP_001394560.1:p.His41Leu	missense
NM_001407632.1:c.122A>T	NP_001394561.1:p.His41Leu	missense
NM_001407633.1:c.122A>T	NP_001394562.1:p.His41Leu	missense
NM_001407634.1:c.122A>T	NP_001394563.1:p.His41Leu	missense
NM_001407635.1:c.122A>T	NP_001394564.1:p.His41Leu	missense
NM_001407636.1:c.122A>T	NP_001394565.1:p.His41Leu	missense
NM_001407637.1:c.122A>T	NP_001394566.1:p.His41Leu	missense
NM_001407638.1:c.122A>T	NP_001394567.1:p.His41Leu	missense
NM_001407639.1:c.122A>T	NP_001394568.1:p.His41Leu	missense
NM_001407640.1:c.122A>T	NP_001394569.1:p.His41Leu	missense
NM_001407641.1:c.122A>T	NP_001394570.1:p.His41Leu	missense
NM_001407642.1:c.122A>T	NP_001394571.1:p.His41Leu	missense
NM_001407644.1:c.122A>T	NP_001394573.1:p.His41Leu	missense
NM_001407645.1:c.122A>T	NP_001394574.1:p.His41Leu	missense
NM_001407646.1:c.122A>T	NP_001394575.1:p.His41Leu	missense
NM_001407647.1:c.122A>T	NP_001394576.1:p.His41Leu	missense
NM_001407648.1:c.122A>T	NP_001394577.1:p.His41Leu	missense
NM_001407649.1:c.122A>T	NP_001394578.1:p.His41Leu	missense
NM_001407652.1:c.122A>T	NP_001394581.1:p.His41Leu	missense
NM_001407653.1:c.122A>T	NP_001394582.1:p.His41Leu	missense
NM_001407654.1:c.122A>T	NP_001394583.1:p.His41Leu	missense
NM_001407655.1:c.122A>T	NP_001394584.1:p.His41Leu	missense
NM_001407656.1:c.122A>T	NP_001394585.1:p.His41Leu	missense
NM_001407657.1:c.122A>T	NP_001394586.1:p.His41Leu	missense
NM_001407658.1:c.122A>T	NP_001394587.1:p.His41Leu	missense
NM_001407659.1:c.122A>T	NP_001394588.1:p.His41Leu	missense
NM_001407660.1:c.122A>T	NP_001394589.1:p.His41Leu	missense
NM_001407661.1:c.122A>T	NP_001394590.1:p.His41Leu	missense
NM_001407662.1:c.122A>T	NP_001394591.1:p.His41Leu	missense
NM_001407663.1:c.122A>T	NP_001394592.1:p.His41Leu	missense
NM_001407664.1:c.122A>T	NP_001394593.1:p.His41Leu	missense
NM_001407665.1:c.122A>T	NP_001394594.1:p.His41Leu	missense
NM_001407666.1:c.122A>T	NP_001394595.1:p.His41Leu	missense
NM_001407667.1:c.122A>T	NP_001394596.1:p.His41Leu	missense
NM_001407668.1:c.122A>T	NP_001394597.1:p.His41Leu	missense
NM_001407669.1:c.122A>T	NP_001394598.1:p.His41Leu	missense
NM_001407670.1:c.122A>T	NP_001394599.1:p.His41Leu	missense
NM_001407671.1:c.122A>T	NP_001394600.1:p.His41Leu	missense
NM_001407672.1:c.122A>T	NP_001394601.1:p.His41Leu	missense
NM_001407673.1:c.122A>T	NP_001394602.1:p.His41Leu	missense
NM_001407674.1:c.122A>T	NP_001394603.1:p.His41Leu	missense
NM_001407675.1:c.122A>T	NP_001394604.1:p.His41Leu	missense
NM_001407676.1:c.122A>T	NP_001394605.1:p.His41Leu	missense
NM_001407677.1:c.122A>T	NP_001394606.1:p.His41Leu	missense
NM_001407678.1:c.122A>T	NP_001394607.1:p.His41Leu	missense
NM_001407679.1:c.122A>T	NP_001394608.1:p.His41Leu	missense
NM_001407680.1:c.122A>T	NP_001394609.1:p.His41Leu	missense
NM_001407681.1:c.122A>T	NP_001394610.1:p.His41Leu	missense
NM_001407682.1:c.122A>T	NP_001394611.1:p.His41Leu	missense
NM_001407683.1:c.122A>T	NP_001394612.1:p.His41Leu	missense
NM_001407684.1:c.122A>T	NP_001394613.1:p.His41Leu	missense
NM_001407685.1:c.122A>T	NP_001394614.1:p.His41Leu	missense
NM_001407686.1:c.122A>T	NP_001394615.1:p.His41Leu	missense
NM_001407687.1:c.122A>T	NP_001394616.1:p.His41Leu	missense
NM_001407688.1:c.122A>T	NP_001394617.1:p.His41Leu	missense
NM_001407689.1:c.122A>T	NP_001394618.1:p.His41Leu	missense
NM_001407690.1:c.122A>T	NP_001394619.1:p.His41Leu	missense
NM_001407691.1:c.122A>T	NP_001394620.1:p.His41Leu	missense
NM_001407694.1:c.-136A>T
NM_001407695.1:c.-140A>T
NM_001407696.1:c.-136A>T
NM_001407697.1:c.-20A>T
NM_001407724.1:c.-136A>T
NM_001407725.1:c.-20A>T
NM_001407727.1:c.-136A>T
NM_001407728.1:c.-20A>T
NM_001407729.1:c.-20A>T
NM_001407730.1:c.-20A>T
NM_001407731.1:c.-136A>T
NM_001407733.1:c.-136A>T
NM_001407734.1:c.-20A>T
NM_001407735.1:c.-20A>T
NM_001407737.1:c.-20A>T
NM_001407739.1:c.-20A>T
NM_001407740.1:c.-20A>T
NM_001407741.1:c.-20A>T
NM_001407743.1:c.-20A>T
NM_001407745.1:c.-20A>T
NM_001407746.1:c.-136A>T
NM_001407748.1:c.-20A>T
NM_001407749.1:c.-136A>T
NM_001407752.1:c.-20A>T
NM_001407838.1:c.-20A>T
NM_001407839.1:c.-20A>T
NM_001407841.1:c.-16A>T
NM_001407842.1:c.-136A>T
NM_001407843.1:c.-136A>T
NM_001407844.1:c.-20A>T
NM_001407846.1:c.-20A>T
NM_001407847.1:c.-20A>T
NM_001407848.1:c.-20A>T
NM_001407850.1:c.-20A>T
NM_001407851.1:c.-20A>T
NM_001407853.1:c.-67A>T
NM_001407854.1:c.122A>T	NP_001394783.1:p.His41Leu	missense
NM_001407858.1:c.122A>T	NP_001394787.1:p.His41Leu	missense
NM_001407859.1:c.122A>T	NP_001394788.1:p.His41Leu	missense
NM_001407860.1:c.122A>T	NP_001394789.1:p.His41Leu	missense
NM_001407861.1:c.122A>T	NP_001394790.1:p.His41Leu	missense
NM_001407862.1:c.122A>T	NP_001394791.1:p.His41Leu	missense
NM_001407863.1:c.122A>T	NP_001394792.1:p.His41Leu	missense
NM_001407874.1:c.122A>T	NP_001394803.1:p.His41Leu	missense
NM_001407875.1:c.122A>T	NP_001394804.1:p.His41Leu	missense
NM_001407879.1:c.-67A>T
NM_001407882.1:c.-67A>T
NM_001407884.1:c.-67A>T
NM_001407885.1:c.-67A>T
NM_001407886.1:c.-67A>T
NM_001407887.1:c.-67A>T
NM_001407889.1:c.-183A>T
NM_001407894.1:c.-67A>T
NM_001407895.1:c.-67A>T
NM_001407896.1:c.-67A>T
NM_001407897.1:c.-67A>T
NM_001407899.1:c.-67A>T
NM_001407900.1:c.-183A>T
NM_001407904.1:c.-67A>T
NM_001407906.1:c.-67A>T
NM_001407907.1:c.-67A>T
NM_001407908.1:c.-67A>T
NM_001407909.1:c.-67A>T
NM_001407910.1:c.-67A>T
NM_001407915.1:c.-67A>T
NM_001407916.1:c.-67A>T
NM_001407917.1:c.-67A>T
NM_001407918.1:c.-67A>T
NM_001407919.1:c.122A>T	NP_001394848.1:p.His41Leu	missense
NM_001407920.1:c.-20A>T
NM_001407921.1:c.-20A>T
NM_001407922.1:c.-20A>T
NM_001407923.1:c.-20A>T
NM_001407926.1:c.-20A>T
NM_001407927.1:c.-20A>T
NM_001407930.1:c.-136A>T
NM_001407933.1:c.-20A>T
NM_001407934.1:c.-20A>T
NM_001407935.1:c.-20A>T
NM_001407937.1:c.122A>T	NP_001394866.1:p.His41Leu	missense
NM_001407938.1:c.122A>T	NP_001394867.1:p.His41Leu	missense
NM_001407939.1:c.122A>T	NP_001394868.1:p.His41Leu	missense
NM_001407940.1:c.122A>T	NP_001394869.1:p.His41Leu	missense
NM_001407941.1:c.122A>T	NP_001394870.1:p.His41Leu	missense
NM_001407942.1:c.-136A>T
NM_001407943.1:c.-20A>T
NM_001407944.1:c.-20A>T
NM_001407946.1:c.-67A>T
NM_001407947.1:c.-67A>T
NM_001407948.1:c.-67A>T
NM_001407949.1:c.-67A>T
NM_001407950.1:c.-67A>T
NM_001407951.1:c.-67A>T
NM_001407952.1:c.-67A>T
NM_001407953.1:c.-67A>T
NM_001407954.1:c.-67A>T
NM_001407955.1:c.-67A>T
NM_001407956.1:c.-67A>T
NM_001407957.1:c.-67A>T
NM_001407958.1:c.-67A>T
NM_001407960.1:c.-182A>T
NM_001407962.1:c.-182A>T
NM_001407964.1:c.-20A>T
NM_001407965.1:c.-298A>T
NM_001407968.1:c.122A>T	NP_001394897.1:p.His41Leu	missense
NM_001407969.1:c.122A>T	NP_001394898.1:p.His41Leu	missense
NM_001407970.1:c.122A>T	NP_001394899.1:p.His41Leu	missense
NM_001407971.1:c.122A>T	NP_001394900.1:p.His41Leu	missense
NM_001407972.1:c.122A>T	NP_001394901.1:p.His41Leu	missense
NM_001407973.1:c.122A>T	NP_001394902.1:p.His41Leu	missense
NM_001407974.1:c.122A>T	NP_001394903.1:p.His41Leu	missense
NM_001407975.1:c.122A>T	NP_001394904.1:p.His41Leu	missense
NM_001407976.1:c.122A>T	NP_001394905.1:p.His41Leu	missense
NM_001407977.1:c.122A>T	NP_001394906.1:p.His41Leu	missense
NM_001407978.1:c.122A>T	NP_001394907.1:p.His41Leu	missense
NM_001407979.1:c.122A>T	NP_001394908.1:p.His41Leu	missense
NM_001407980.1:c.122A>T	NP_001394909.1:p.His41Leu	missense
NM_001407981.1:c.122A>T	NP_001394910.1:p.His41Leu	missense
NM_001407982.1:c.122A>T	NP_001394911.1:p.His41Leu	missense
NM_001407983.1:c.122A>T	NP_001394912.1:p.His41Leu	missense
NM_001407984.1:c.122A>T	NP_001394913.1:p.His41Leu	missense
NM_001407985.1:c.122A>T	NP_001394914.1:p.His41Leu	missense
NM_001407986.1:c.122A>T	NP_001394915.1:p.His41Leu	missense
NM_001407990.1:c.122A>T	NP_001394919.1:p.His41Leu	missense
NM_001407991.1:c.122A>T	NP_001394920.1:p.His41Leu	missense
NM_001407992.1:c.122A>T	NP_001394921.1:p.His41Leu	missense
NM_001407993.1:c.122A>T	NP_001394922.1:p.His41Leu	missense
NM_001408392.1:c.122A>T	NP_001395321.1:p.His41Leu	missense
NM_001408396.1:c.122A>T	NP_001395325.1:p.His41Leu	missense
NM_001408397.1:c.122A>T	NP_001395326.1:p.His41Leu	missense
NM_001408398.1:c.122A>T	NP_001395327.1:p.His41Leu	missense
NM_001408399.1:c.122A>T	NP_001395328.1:p.His41Leu	missense
NM_001408400.1:c.122A>T	NP_001395329.1:p.His41Leu	missense
NM_001408401.1:c.122A>T	NP_001395330.1:p.His41Leu	missense
NM_001408402.1:c.122A>T	NP_001395331.1:p.His41Leu	missense
NM_001408403.1:c.122A>T	NP_001395332.1:p.His41Leu	missense
NM_001408404.1:c.122A>T	NP_001395333.1:p.His41Leu	missense
NM_001408406.1:c.122A>T	NP_001395335.1:p.His41Leu	missense
NM_001408407.1:c.122A>T	NP_001395336.1:p.His41Leu	missense
NM_001408408.1:c.122A>T	NP_001395337.1:p.His41Leu	missense
NM_001408409.1:c.122A>T	NP_001395338.1:p.His41Leu	missense
NM_001408410.1:c.-20A>T
NM_001408411.1:c.122A>T	NP_001395340.1:p.His41Leu	missense
NM_001408412.1:c.122A>T	NP_001395341.1:p.His41Leu	missense
NM_001408413.1:c.122A>T	NP_001395342.1:p.His41Leu	missense
NM_001408414.1:c.122A>T	NP_001395343.1:p.His41Leu	missense
NM_001408415.1:c.122A>T	NP_001395344.1:p.His41Leu	missense
NM_001408416.1:c.122A>T	NP_001395345.1:p.His41Leu	missense
NM_001408418.1:c.122A>T	NP_001395347.1:p.His41Leu	missense
NM_001408419.1:c.122A>T	NP_001395348.1:p.His41Leu	missense
NM_001408420.1:c.122A>T	NP_001395349.1:p.His41Leu	missense
NM_001408421.1:c.122A>T	NP_001395350.1:p.His41Leu	missense
NM_001408422.1:c.122A>T	NP_001395351.1:p.His41Leu	missense
NM_001408423.1:c.122A>T	NP_001395352.1:p.His41Leu	missense
NM_001408424.1:c.122A>T	NP_001395353.1:p.His41Leu	missense
NM_001408425.1:c.122A>T	NP_001395354.1:p.His41Leu	missense
NM_001408426.1:c.122A>T	NP_001395355.1:p.His41Leu	missense
NM_001408427.1:c.122A>T	NP_001395356.1:p.His41Leu	missense
NM_001408428.1:c.122A>T	NP_001395357.1:p.His41Leu	missense
NM_001408429.1:c.122A>T	NP_001395358.1:p.His41Leu	missense
NM_001408430.1:c.122A>T	NP_001395359.1:p.His41Leu	missense
NM_001408431.1:c.122A>T	NP_001395360.1:p.His41Leu	missense
NM_001408432.1:c.122A>T	NP_001395361.1:p.His41Leu	missense
NM_001408433.1:c.122A>T	NP_001395362.1:p.His41Leu	missense
NM_001408434.1:c.122A>T	NP_001395363.1:p.His41Leu	missense
NM_001408435.1:c.122A>T	NP_001395364.1:p.His41Leu	missense
NM_001408436.1:c.122A>T	NP_001395365.1:p.His41Leu	missense
NM_001408437.1:c.122A>T	NP_001395366.1:p.His41Leu	missense
NM_001408438.1:c.122A>T	NP_001395367.1:p.His41Leu	missense
NM_001408439.1:c.122A>T	NP_001395368.1:p.His41Leu	missense
NM_001408440.1:c.122A>T	NP_001395369.1:p.His41Leu	missense
NM_001408441.1:c.122A>T	NP_001395370.1:p.His41Leu	missense
NM_001408442.1:c.122A>T	NP_001395371.1:p.His41Leu	missense
NM_001408443.1:c.122A>T	NP_001395372.1:p.His41Leu	missense
NM_001408444.1:c.122A>T	NP_001395373.1:p.His41Leu	missense
NM_001408445.1:c.122A>T	NP_001395374.1:p.His41Leu	missense
NM_001408446.1:c.122A>T	NP_001395375.1:p.His41Leu	missense
NM_001408447.1:c.122A>T	NP_001395376.1:p.His41Leu	missense
NM_001408448.1:c.122A>T	NP_001395377.1:p.His41Leu	missense
NM_001408450.1:c.122A>T	NP_001395379.1:p.His41Leu	missense
NM_001408452.1:c.-20A>T
NM_001408453.1:c.-20A>T
NM_001408455.1:c.-136A>T
NM_001408456.1:c.-136A>T
NM_001408458.1:c.-20A>T
NM_001408462.1:c.-20A>T
NM_001408463.1:c.-20A>T
NM_001408465.1:c.-140A>T
NM_001408466.1:c.-20A>T
NM_001408468.1:c.-136A>T
NM_001408469.1:c.-20A>T
NM_001408470.1:c.-20A>T
NM_001408472.1:c.122A>T	NP_001395401.1:p.His41Leu	missense
NM_001408473.1:c.122A>T	NP_001395402.1:p.His41Leu	missense
NM_001408474.1:c.122A>T	NP_001395403.1:p.His41Leu	missense
NM_001408475.1:c.122A>T	NP_001395404.1:p.His41Leu	missense
NM_001408476.1:c.122A>T	NP_001395405.1:p.His41Leu	missense
NM_001408478.1:c.-67A>T
NM_001408479.1:c.-67A>T
NM_001408480.1:c.-67A>T
NM_001408481.1:c.-67A>T
NM_001408482.1:c.-67A>T
NM_001408483.1:c.-67A>T
NM_001408484.1:c.-67A>T
NM_001408485.1:c.-67A>T
NM_001408489.1:c.-67A>T
NM_001408490.1:c.-67A>T
NM_001408491.1:c.-67A>T
NM_001408492.1:c.-183A>T
NM_001408493.1:c.-67A>T
NM_001408494.1:c.122A>T	NP_001395423.1:p.His41Leu	missense
NM_001408495.1:c.122A>T	NP_001395424.1:p.His41Leu	missense
NM_001408497.1:c.-20A>T
NM_001408499.1:c.-20A>T
NM_001408500.1:c.-20A>T
NM_001408501.1:c.-136A>T
NM_001408502.1:c.-67A>T
NM_001408503.1:c.-20A>T
NM_001408504.1:c.-20A>T
NM_001408505.1:c.-20A>T
NM_001408506.1:c.-67A>T
NM_001408507.1:c.-67A>T
NM_001408508.1:c.-67A>T
NM_001408509.1:c.-67A>T
NM_001408510.1:c.-182A>T
NM_001408512.1:c.-182A>T
NM_001408513.1:c.-67A>T
NM_001408514.1:c.-67A>T
NM_007297.4:c.-8+8279A>T		intron variant
NM_007298.4:c.122A>T	NP_009229.2:p.His41Leu	missense
NM_007299.4:c.122A>T	NP_009230.2:p.His41Leu	missense
NM_007300.4:c.122A>T	NP_009231.2:p.His41Leu	missense
NM_007304.2:c.122A>T	NP_009235.2:p.His41Leu	missense
NR_027676.2:n.324A>T		non-coding transcript variant
NC_000017.11:g.43115738T>A
NC_000017.10:g.41267755T>A
NG_005905.2:g.102246A>T
LRG_292:g.102246A>T
LRG_292t1:c.122A>T	LRG_292p1:p.His41Leu

... more HGVS ... less HGVS

Protein change

H41L

Other names

Canonical SPDI

NC_000017.11:43115737:T:A

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

functionally_abnormal; Sequence Ontology [ SO:0002218]

The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.122A>T, a MISSENSE variant, produced a function score of -1.78, corresponding to a functional classification of LOSS_OF_FUNCTION. 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: CA10580711 dbSNP: rs80357276 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 cancer-predisposing syndrome	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 11, 2021	RCV000221074.9
Breast-ovarian cancer, familial, susceptibility to, 1	Likely pathogenic (3)	criteria provided, single submitter	Oct 17, 2022	RCV000238698.8
not provided	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jan 3, 2022	RCV000484008.4
Hereditary breast ovarian cancer syndrome	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Aug 25, 2023	RCV001194451.11
Fanconi anemia, complementation group S	Likely pathogenic (1)	criteria provided, single submitter	Jan 13, 2020	RCV001292947.2

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.
Pathogenic (Jun 11, 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: SCV000274542.7 First in ClinVar: May 29, 2016 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 16403807‚ 25823446‚ 30209399 Comment: The p.H41L pathogenic mutation (also known as c.122A>T), located in coding exon 2 of the BRCA1 gene, results from an A to T substitution at … (more) The p.H41L pathogenic mutation (also known as c.122A>T), located in coding exon 2 of the BRCA1 gene, results from an A to T substitution at nucleotide position 122. The histidine at codon 41 is replaced by leucine, an amino acid with similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay. (Findlay GM et al. Nature. 2018 10;562:217-222). Substitutions at this amino acid residue severely impact E3 ubiquitin ligase activity, however, they have minimal impact on BARD1 binding (Morris JR et al. Hum Mol Genet. 2006 Feb;15(4):599-606; Starita LM et al. Genetics. 2015 Jun;200:413-22). Several other substitutions at this amino acid position are pathogenic, including arginine and tyrosine (Ambry internal data; Morris JR et al. Hum. Mol. Genet. 2006 Feb; 15(4):599-606; Ransburgh DJ et al. Cancer Res. 2010 Feb; 70(3):988-95; Towler WI et al. Hum. Mutat. 2013 Mar; 34(3):439-45). This variant affects a known zinc binding motif which is predicted to disrupt protein folding (Ambry internal data; Brzovic PS et al. Nat. Struct. Biol. 2001 Oct;8:833-7; Brzovic PS et al. Proc. Natl. Acad. Sci. U.S.A., 2003 May;100:5646-51). 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 (Jan 03, 2022)	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: SCV000296354.3 First in ClinVar: Aug 01, 2016 Last updated: Sep 29, 2024	Publications: PubMed (6) PubMed: 26295337‚ 25186627‚ 30219179‚ 16403807‚ 30209399‚ 25823446 Comment: This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a woman affected … (more) This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a woman affected with breast cancer (PMID: 25186627 (2015)). Functional studies have shown that this variant causes loss of DNA repair activity and reduced cellular survival (PMID: 30209399 (2018), 30219179 (2018)), as well as reduced E3 ligase activity (PMID: 25823446 (2015)). Based on the available information, this variant is classified as pathogenic. (less)
Likely pathogenic (Jul 17, 2017)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000564710.5 First in ClinVar: Apr 27, 2017 Last updated: Dec 19, 2017	Comment: This variant is denoted BRCA1 c.122A>T at the cDNA level, p.His41Leu (H41L) at the protein level, and results in the change of a Histidine to … (more) This variant is denoted BRCA1 c.122A>T at the cDNA level, p.His41Leu (H41L) at the protein level, and results in the change of a Histidine to a Leucine (CAC>CTC). Using alternate nomenclature, this variant would be defined as BRCA1 241A>T. Functional interrogation of BRCA1 His41Leu by yeast-hybrid assay demonstrates impaired interaction between the variant and E2 (UbcH5a) in comparison to wild type (Morris 2006). In addition, a less severe, conservative amino acid change BRCA1 His41Arg (H41R) was predicted to be pathogenic by a multifactorial model based on pathology, species conservation and familial co-segregation, was deficient in a single strand annealing assay, has been associated with centrosome amplification, was non-functional in a homology-directed recombination (HDR) assay and exhibited decreased BARD1 binding and ubiquitin ligase activity (Whiley 2014, Towler 2013, Kais 2012, Ransburgh 2010, Morris 2006). BRCA1 His41Leu was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Histidine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 His41Leu occurs at a position that is conserved in mammals and is located in the RING-finger domain and Ub site, as well as a region known to interact with multiple other proteins (Wu 1996, Narod 2004, Borg 2010, Harte 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available information, we consider BRCA1 His41Leu to be a likely pathogenic variant. (less)
Likely pathogenic (Jan 13, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Fanconi anemia, complementation group S Affected status: yes Allele origin: maternal	Baylor Genetics Study: CSER-TexasKidsCanSeq Accession: SCV001481655.2 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021	Publications: PubMed (2) PubMed: 25186627‚ 30209399 Comment: This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 25186627, 30209399]
Likely pathogenic (Feb 10, 2020)	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: SCV001348623.2 First in ClinVar: Mar 25, 2020 Last updated: Jan 12, 2022	Comment: This missense variant replaces histidine with leucine at codon 41 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more) This missense variant replaces histidine with leucine at codon 41 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional studies have shown that this variant is non-functional in a homology-direct repair assay (PMID: 30219179) and in a haploid cell proliferation assay (PMID: 30209399) and disrupts binding to E2 ubiquitin conjugating enzyme (PMID: 16403807). This variant has been reported in an individual affected with breast cancer (PMID: 25186627). A different variant occurring at the same position, p.His41Arg, is classified as Pathogenic (Clinvar variation ID: 54166), suggesting that histidine at this position is important for BRCA1 function. 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 Likely Pathogenic. (less)
Pathogenic (Jan 30, 2023)	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: SCV001364030.3 First in ClinVar: Jun 22, 2020 Last updated: Nov 11, 2023	Publications: PubMed (5) PubMed: 16403807‚ 25186627‚ 30209399‚ 30219179‚ 34413315 Comment: Variant summary: BRCA1 c.122A>T (p.His41Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging … (more) Variant summary: BRCA1 c.122A>T (p.His41Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250784 control chromosomes. c.122A>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Tung_2014, Herzog_2021). These data indicate that the variant is likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed a damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Other variants impacting the same codon have been classified as pathogenic by our lab (p.His41Arg). Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (5 likely pathogenic/pathogenic, 2 VUS). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Aug 25, 2023)	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: SCV001392328.5 First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024	Publications: PubMed (7) PubMed: 25186627‚ 30209399‚ 25823446‚ 30219179‚ 20103620‚ 21725363‚ 24489791 Comment: This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 41 of the BRCA1 protein (p.His41Leu). … (more) This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 41 of the BRCA1 protein (p.His41Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 230862). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25823446, 30209399, 30219179). This variant disrupts the p.His41 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20103620, 21725363, 24489791, 25823446, 30209399). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
Likely pathogenic (Oct 17, 2022)	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: SCV004216897.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
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: SCV001237887.1 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: LOSS_OF_FUNCTION:-1.77532347459198
Uncertain significance (Nov 21, 2017)	Flagged submission flagged submission (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000784758.2 First in ClinVar: Aug 01, 2016 Last updated: Aug 01, 2016	Publications: PubMed (2) PubMed: 25186627‚ 16403807
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

Comment:

The p.H41L pathogenic mutation (also known as c.122A>T), located in coding exon 2 of the BRCA1 gene, results from an A to T substitution at nucleotide position 122. The histidine at codon 41 is replaced by leucine, an amino acid with similar properties. One functional study found that this nucleotide substitution is non-functional in a high-throughput, genome editing, haploid cell survival assay. (Findlay GM et al. Nature. 2018 10;562:217-222). Substitutions at this amino acid residue severely impact E3 ubiquitin ligase activity, however, they have minimal impact on BARD1 binding (Morris JR et al. Hum Mol Genet. 2006 Feb;15(4):599-606; Starita LM et al. Genetics. 2015 Jun;200:413-22). Several other substitutions at this amino acid position are pathogenic, including arginine and tyrosine (Ambry internal data; Morris JR et al. Hum. Mol. Genet. 2006 Feb; 15(4):599-606; Ransburgh DJ et al. Cancer Res. 2010 Feb; 70(3):988-95; Towler WI et al. Hum. Mutat. 2013 Mar; 34(3):439-45). This variant affects a known zinc binding motif which is predicted to disrupt protein folding (Ambry internal data; Brzovic PS et al. Nat. Struct. Biol. 2001 Oct;8:833-7; Brzovic PS et al. Proc. Natl. Acad. Sci. U.S.A., 2003 May;100:5646-51). 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:

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a woman affected with breast cancer (PMID: 25186627 (2015)). Functional studies have shown that this variant causes loss of DNA repair activity and reduced cellular survival (PMID: 30209399 (2018), 30219179 (2018)), as well as reduced E3 ligase activity (PMID: 25823446 (2015)). Based on the available information, this variant is classified as pathogenic.

Comment:

This variant is denoted BRCA1 c.122A>T at the cDNA level, p.His41Leu (H41L) at the protein level, and results in the change of a Histidine to a Leucine (CAC>CTC). Using alternate nomenclature, this variant would be defined as BRCA1 241A>T. Functional interrogation of BRCA1 His41Leu by yeast-hybrid assay demonstrates impaired interaction between the variant and E2 (UbcH5a) in comparison to wild type (Morris 2006). In addition, a less severe, conservative amino acid change BRCA1 His41Arg (H41R) was predicted to be pathogenic by a multifactorial model based on pathology, species conservation and familial co-segregation, was deficient in a single strand annealing assay, has been associated with centrosome amplification, was non-functional in a homology-directed recombination (HDR) assay and exhibited decreased BARD1 binding and ubiquitin ligase activity (Whiley 2014, Towler 2013, Kais 2012, Ransburgh 2010, Morris 2006). BRCA1 His41Leu was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Histidine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA1 His41Leu occurs at a position that is conserved in mammals and is located in the RING-finger domain and Ub site, as well as a region known to interact with multiple other proteins (Wu 1996, Narod 2004, Borg 2010, Harte 2010, Paul 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available information, we consider BRCA1 His41Leu to be a likely pathogenic variant.

Comment:

This missense variant replaces histidine with leucine at codon 41 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional studies have shown that this variant is non-functional in a homology-direct repair assay (PMID: 30219179) and in a haploid cell proliferation assay (PMID: 30209399) and disrupts binding to E2 ubiquitin conjugating enzyme (PMID: 16403807). This variant has been reported in an individual affected with breast cancer (PMID: 25186627). A different variant occurring at the same position, p.His41Arg, is classified as Pathogenic (Clinvar variation ID: 54166), suggesting that histidine at this position is important for BRCA1 function. 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 Likely Pathogenic.

Comment:

Variant summary: BRCA1 c.122A>T (p.His41Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250784 control chromosomes. c.122A>T has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Tung_2014, Herzog_2021). These data indicate that the variant is likely to be associated with disease. At least one functional study reports experimental evidence evaluating an impact on protein function and showed a damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. Other variants impacting the same codon have been classified as pathogenic by our lab (p.His41Arg). Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (5 likely pathogenic/pathogenic, 2 VUS). Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 41 of the BRCA1 protein (p.His41Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 25186627). ClinVar contains an entry for this variant (Variation ID: 230862). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25823446, 30209399, 30219179). This variant disrupts the p.His41 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20103620, 21725363, 24489791, 25823446, 30209399). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as 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.
functionally_abnormal (SO:0002218)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	LOSS_OF_FUNCTION:-1.77532347459198	Brotman Baty Institute, University of Washington Accession: SCV001237887.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.122A>T, a MISSENSE variant, produced a function score of -1.78, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.122A>T, a MISSENSE variant, produced a function score of -1.78, corresponding to a functional classification of LOSS_OF_FUNCTION. 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
Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America.	Herzog JS	NPJ breast cancer	2021	PMID: 34413315
A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function.	Starita LM	American journal of human genetics	2018	PMID: 30219179
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.	Starita LM	Genetics	2015	PMID: 25823446
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.	Tung N	Cancer	2015	PMID: 25186627
Multifactorial likelihood assessment of BRCA1 and BRCA2 missense variants confirms that BRCA1:c.122A>G(p.His41Arg) is a pathogenic mutation.	Whiley PJ	PloS one	2014	PMID: 24489791
Functional differences among BRCA1 missense mutations in the control of centrosome duplication.	Kais Z	Oncogene	2012	PMID: 21725363
Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination.	Ransburgh DJ	Cancer research	2010	PMID: 20103620
Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility.	Morris JR	Human molecular genetics	2006	PMID: 16403807
https://sge.gs.washington.edu/BRCA1/	-	-	-	-

Text-mined citations for rs80357276 ...

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 Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.122A>T (p.His41Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80357276 ...