NM_014000.3(VCL):c.829C>A (p.Leu277Met) AND Dilated cardiomyopathy 1W

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 4, 2022
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:: RCV000645321.6

Allele description [Variation Report for NM_014000.3(VCL):c.829C>A (p.Leu277Met)]

NM_014000.3(VCL):c.829C>A (p.Leu277Met)

Gene:

VCL:vinculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.2

Genomic location:

Preferred name:

NM_014000.3(VCL):c.829C>A (p.Leu277Met)

HGVS:

NC_000010.11:g.74082499C>A
NG_008868.1:g.89386C>A
NM_003373.4:c.829C>A
NM_014000.3:c.829C>AMANE SELECT
NP_003364.1:p.Leu277Met
NP_054706.1:p.Leu277Met
NP_054706.1:p.Leu277Met
LRG_383t1:c.829C>A
LRG_383:g.89386C>A
LRG_383p1:p.Leu277Met
NC_000010.10:g.75842257C>A
NM_014000.2:c.829C>A
P18206:p.Leu277Met

Protein change:

L277M; LEU277MET

Links:

UniProtKB: P18206#VAR_035101; OMIM: 193065.0003; dbSNP: rs71579353

NCBI 1000 Genomes Browser:

rs71579353

Molecular consequence:

NM_003373.4:c.829C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014000.3:c.829C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1W (CMD1W)
Identifiers:: MONDO: MONDO:0012667; MedGen: C1969639; Orphanet: 154; OMIM: 611407

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000767064	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 4, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16712796, 24503780, 27930701, 31513939, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000767064

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 4, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.

Vasile VC, Ommen SR, Edwards WD, Ackerman MJ.

Biochem Biophys Res Commun. 2006 Jul 7;345(3):998-1003. Epub 2006 May 4.

PubMed [citation]

PMID:: 16712796

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000767064.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 277 of the VCL protein (p.Leu277Met). This variant is present in population databases (rs71579353, gnomAD 0.02%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 16712796, 24503780, 27930701, 31513939). ClinVar contains an entry for this variant (Variation ID: 12198). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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