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NM_014000.3(VCL):c.695T>A (p.Phe232Tyr) AND Dilated cardiomyopathy 1W

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 19, 2023
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:
RCV000686012.7

Allele description [Variation Report for NM_014000.3(VCL):c.695T>A (p.Phe232Tyr)]

NM_014000.3(VCL):c.695T>A (p.Phe232Tyr)

Gene:
VCL:vinculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.2
Genomic location:
Preferred name:
NM_014000.3(VCL):c.695T>A (p.Phe232Tyr)
HGVS:
  • NC_000010.11:g.74074815T>A
  • NG_008868.1:g.81702T>A
  • NM_003373.4:c.695T>A
  • NM_014000.3:c.695T>AMANE SELECT
  • NP_003364.1:p.Phe232Tyr
  • NP_054706.1:p.Phe232Tyr
  • NP_054706.1:p.Phe232Tyr
  • LRG_383t1:c.695T>A
  • LRG_383:g.81702T>A
  • LRG_383p1:p.Phe232Tyr
  • NC_000010.10:g.75834573T>A
  • NM_014000.2:c.695T>A
Protein change:
F232Y
Links:
dbSNP: rs200956572
NCBI 1000 Genomes Browser:
rs200956572
Molecular consequence:
  • NM_003373.4:c.695T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014000.3:c.695T>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000813515Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 19, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]
PMID:
30847666
PMCID:
PMC6533346

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000813515.4

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

Description

This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 232 of the VCL protein (p.Phe232Tyr). This variant is present in population databases (rs200956572, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of VCL-related conditions (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 192101). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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

Last Updated: Sep 29, 2024