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NM_014000.3(VCL):c.2468G>A (p.Arg823Gln) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Jan 2, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003987451.1

Allele description [Variation Report for NM_014000.3(VCL):c.2468G>A (p.Arg823Gln)]

NM_014000.3(VCL):c.2468G>A (p.Arg823Gln)

Gene:
VCL:vinculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.2
Genomic location:
Preferred name:
NM_014000.3(VCL):c.2468G>A (p.Arg823Gln)
HGVS:
  • NC_000010.11:g.74107263G>A
  • NG_008868.1:g.114150G>A
  • NM_003373.4:c.2468G>A
  • NM_014000.3:c.2468G>AMANE SELECT
  • NP_003364.1:p.Arg823Gln
  • NP_054706.1:p.Arg823Gln
  • NP_054706.1:p.Arg823Gln
  • LRG_383t1:c.2468G>A
  • LRG_383:g.114150G>A
  • LRG_383p1:p.Arg823Gln
  • NC_000010.10:g.75867021G>A
  • NM_014000.2:c.2468G>A
Protein change:
R823Q
Links:
dbSNP: rs759202535
NCBI 1000 Genomes Browser:
rs759202535
Molecular consequence:
  • NM_003373.4:c.2468G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014000.3:c.2468G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004803457Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely benign
(Jan 2, 2024)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.

Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes TJW, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AY, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, et al.

Circulation. 2020 Feb 4;141(5):387-398. doi: 10.1161/CIRCULATIONAHA.119.037661. Epub 2020 Jan 27.

PubMed [citation]
PMID:
31983221
PMCID:
PMC7004454

Implications of Genetic Testing in Dilated Cardiomyopathy.

Verdonschot JAJ, Hazebroek MR, Krapels IPC, Henkens MTHM, Raafs A, Wang P, Merken JJ, Claes GRF, Vanhoutte EK, van den Wijngaard A, Heymans SRB, Brunner HG.

Circ Genom Precis Med. 2020 Oct;13(5):476-487. doi: 10.1161/CIRCGEN.120.003031. Epub 2020 Sep 3.

PubMed [citation]
PMID:
32880476

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004803457.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: VCL c.2468G>A (p.Arg823Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.6e-05 in 282852 control chromosomes, predominantly at a frequency of 8.5e-05 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in VCL causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.2468G>A has been reported in the literature in individuals affected with Dilated cardiomyopathy (Mazzarotto_2020, Verdonschot_2020). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31983221, 32880476). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024