VCV001209130.6 - ClinVar

NM_001376571.1(MADD):c.509G>A (p.Arg170His)

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.

(2)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001376571.1(MADD):c.509G>A (p.Arg170His)

Variation ID: 1209130 Accession: VCV001209130.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p11.2 11: 47275009 (GRCh38) [ NCBI UCSC ] 11: 47296560 (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 21, 2021	May 1, 2024	Sep 7, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001376571.1:c.509G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001363500.1:p.Arg170His	missense
NM_001135943.2:c.509G>A	NP_001129415.1:p.Arg170His	missense
NM_001135944.2:c.509G>A	NP_001129416.1:p.Arg170His	missense
NM_001376572.1:c.509G>A	NP_001363501.1:p.Arg170His	missense
NM_001376573.1:c.509G>A	NP_001363502.1:p.Arg170His	missense
NM_001376574.1:c.509G>A	NP_001363503.1:p.Arg170His	missense
NM_001376575.1:c.509G>A	NP_001363504.1:p.Arg170His	missense
NM_001376576.1:c.509G>A	NP_001363505.1:p.Arg170His	missense
NM_001376577.1:c.509G>A	NP_001363506.1:p.Arg170His	missense
NM_001376578.1:c.509G>A	NP_001363507.1:p.Arg170His	missense
NM_001376579.1:c.509G>A	NP_001363508.1:p.Arg170His	missense
NM_001376580.1:c.509G>A	NP_001363509.1:p.Arg170His	missense
NM_001376581.1:c.509G>A	NP_001363510.1:p.Arg170His	missense
NM_001376582.1:c.509G>A	NP_001363511.1:p.Arg170His	missense
NM_001376583.1:c.509G>A	NP_001363512.1:p.Arg170His	missense
NM_001376584.1:c.509G>A	NP_001363513.1:p.Arg170His	missense
NM_001376585.1:c.509G>A	NP_001363514.1:p.Arg170His	missense
NM_001376586.1:c.509G>A	NP_001363515.1:p.Arg170His	missense
NM_001376593.1:c.509G>A	NP_001363522.1:p.Arg170His	missense
NM_001376594.1:c.509G>A	NP_001363523.1:p.Arg170His	missense
NM_001376595.1:c.509G>A	NP_001363524.1:p.Arg170His	missense
NM_001376596.1:c.509G>A	NP_001363525.1:p.Arg170His	missense
NM_001376597.1:c.509G>A	NP_001363526.1:p.Arg170His	missense
NM_001376598.1:c.509G>A	NP_001363527.1:p.Arg170His	missense
NM_001376599.1:c.509G>A	NP_001363528.1:p.Arg170His	missense
NM_001376600.1:c.509G>A	NP_001363529.1:p.Arg170His	missense
NM_001376601.1:c.509G>A	NP_001363530.1:p.Arg170His	missense
NM_001376602.1:c.509G>A	NP_001363531.1:p.Arg170His	missense
NM_001376603.1:c.509G>A	NP_001363532.1:p.Arg170His	missense
NM_001376604.1:c.509G>A	NP_001363533.1:p.Arg170His	missense
NM_001376605.1:c.509G>A	NP_001363534.1:p.Arg170His	missense
NM_001376606.1:c.509G>A	NP_001363535.1:p.Arg170His	missense
NM_001376607.1:c.509G>A	NP_001363536.1:p.Arg170His	missense
NM_001376608.1:c.509G>A	NP_001363537.1:p.Arg170His	missense
NM_001376609.1:c.509G>A	NP_001363538.1:p.Arg170His	missense
NM_001376610.1:c.509G>A	NP_001363539.1:p.Arg170His	missense
NM_001376611.1:c.509G>A	NP_001363540.1:p.Arg170His	missense
NM_001376612.1:c.509G>A	NP_001363541.1:p.Arg170His	missense
NM_001376613.1:c.509G>A	NP_001363542.1:p.Arg170His	missense
NM_001376614.1:c.509G>A	NP_001363543.1:p.Arg170His	missense
NM_001376615.1:c.509G>A	NP_001363544.1:p.Arg170His	missense
NM_001376616.1:c.509G>A	NP_001363545.1:p.Arg170His	missense
NM_001376617.1:c.509G>A	NP_001363546.1:p.Arg170His	missense
NM_001376618.1:c.509G>A	NP_001363547.1:p.Arg170His	missense
NM_001376619.1:c.509G>A	NP_001363548.1:p.Arg170His	missense
NM_001376620.1:c.305G>A	NP_001363549.1:p.Arg102His	missense
NM_001376621.1:c.509G>A	NP_001363550.1:p.Arg170His	missense
NM_001376622.1:c.509G>A	NP_001363551.1:p.Arg170His	missense
NM_001376623.1:c.509G>A	NP_001363552.1:p.Arg170His	missense
NM_001376624.1:c.509G>A	NP_001363553.1:p.Arg170His	missense
NM_001376625.1:c.509G>A	NP_001363554.1:p.Arg170His	missense
NM_001376626.1:c.305G>A	NP_001363555.1:p.Arg102His	missense
NM_001376627.1:c.305G>A	NP_001363556.1:p.Arg102His	missense
NM_001376628.1:c.509G>A	NP_001363557.1:p.Arg170His	missense
NM_001376629.1:c.509G>A	NP_001363558.1:p.Arg170His	missense
NM_001376630.1:c.509G>A	NP_001363559.1:p.Arg170His	missense
NM_001376631.1:c.509G>A	NP_001363560.1:p.Arg170His	missense
NM_001376632.1:c.509G>A	NP_001363561.1:p.Arg170His	missense
NM_001376633.1:c.509G>A	NP_001363562.1:p.Arg170His	missense
NM_001376634.1:c.509G>A	NP_001363563.1:p.Arg170His	missense
NM_001376635.1:c.305G>A	NP_001363564.1:p.Arg102His	missense
NM_001376636.1:c.509G>A	NP_001363565.1:p.Arg170His	missense
NM_001376637.1:c.509G>A	NP_001363566.1:p.Arg170His	missense
NM_001376638.1:c.509G>A	NP_001363567.1:p.Arg170His	missense
NM_001376639.1:c.509G>A	NP_001363568.1:p.Arg170His	missense
NM_001376640.1:c.509G>A	NP_001363569.1:p.Arg170His	missense
NM_001376641.1:c.509G>A	NP_001363570.1:p.Arg170His	missense
NM_001376642.1:c.509G>A	NP_001363571.1:p.Arg170His	missense
NM_001376643.1:c.509G>A	NP_001363572.1:p.Arg170His	missense
NM_001376644.1:c.305G>A	NP_001363573.1:p.Arg102His	missense
NM_001376645.1:c.509G>A	NP_001363574.1:p.Arg170His	missense
NM_001376646.1:c.305G>A	NP_001363575.1:p.Arg102His	missense
NM_001376647.1:c.305G>A	NP_001363576.1:p.Arg102His	missense
NM_001376648.1:c.305G>A	NP_001363577.1:p.Arg102His	missense
NM_001376649.1:c.509G>A	NP_001363578.1:p.Arg170His	missense
NM_001376650.1:c.509G>A	NP_001363579.1:p.Arg170His	missense
NM_001376651.1:c.509G>A	NP_001363580.1:p.Arg170His	missense
NM_001376652.1:c.509G>A	NP_001363581.1:p.Arg170His	missense
NM_001376653.1:c.509G>A	NP_001363582.1:p.Arg170His	missense
NM_001376654.1:c.305G>A	NP_001363583.1:p.Arg102His	missense
NM_001376655.1:c.509G>A	NP_001363584.1:p.Arg170His	missense
NM_001376656.1:c.509G>A	NP_001363585.1:p.Arg170His	missense
NM_001376657.1:c.305G>A	NP_001363586.1:p.Arg102His	missense
NM_001376658.1:c.509G>A	NP_001363587.1:p.Arg170His	missense
NM_001376659.1:c.305G>A	NP_001363588.1:p.Arg102His	missense
NM_001376660.1:c.305G>A	NP_001363589.1:p.Arg102His	missense
NM_001376661.1:c.509G>A	NP_001363590.1:p.Arg170His	missense
NM_001376662.1:c.509G>A	NP_001363591.1:p.Arg170His	missense
NM_001376663.1:c.-7-890G>A		intron variant
NM_003682.4:c.509G>A	NP_003673.3:p.Arg170His	missense
NM_130470.3:c.509G>A	NP_569826.2:p.Arg170His	missense
NM_130471.3:c.509G>A	NP_569827.2:p.Arg170His	missense
NM_130472.3:c.509G>A	NP_569828.2:p.Arg170His	missense
NM_130473.3:c.509G>A	NP_569829.2:p.Arg170His	missense
NM_130474.3:c.509G>A	NP_569830.2:p.Arg170His	missense
NM_130475.3:c.509G>A	NP_569831.1:p.Arg170His	missense
NM_130476.3:c.509G>A	NP_569832.2:p.Arg170His	missense
NR_164835.1:n.711G>A		non-coding transcript variant
NR_164836.1:n.711G>A		non-coding transcript variant
NR_164837.1:n.711G>A		non-coding transcript variant
NR_164838.1:n.561G>A		non-coding transcript variant
NR_164839.1:n.711G>A		non-coding transcript variant
NR_164840.1:n.711G>A		non-coding transcript variant
NR_164841.1:n.711G>A		non-coding transcript variant
NR_164842.1:n.711G>A		non-coding transcript variant
NC_000011.10:g.47275009G>A
NC_000011.9:g.47296560G>A
NG_029462.1:g.10634G>A

... more HGVS ... less HGVS

Protein change

R102H, R170H

Other names

Canonical SPDI

NC_000011.10:47275008:G:A

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

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.

The Genome Aggregation Database (gnomAD) 0.00004

Trans-Omics for Precision Medicine (TOPMed) 0.00006

Links

dbSNP: rs752898668 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.
MADD		-	-	GRCh38 GRCh37	243	260

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.
not provided	Uncertain significance (1)	criteria provided, single submitter	Feb 26, 2021	RCV001577696.3
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Sep 7, 2022	RCV002568498.2

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.
Uncertain significance (Feb 26, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001805120.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021	Comment: In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our … (more) In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge (less)
Uncertain significance (Sep 07, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV003704645.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: The c.509G>A (p.R170H) alteration is located in exon 3 (coding exon 2) of the MADD gene. This alteration results from a G to A substitution … (more) The c.509G>A (p.R170H) alteration is located in exon 3 (coding exon 2) of the MADD gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)

Comment:

The c.509G>A (p.R170H) alteration is located in exon 3 (coding exon 2) of the MADD gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs752898668 ...

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 May 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001376571.1(MADD):c.509G>A (p.Arg170His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs752898668 ...