NM_014000.3(VCL):c.2828_2829del (p.Pro943fs) AND Primary dilated cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 27, 2015
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:: RCV000219138.4

Allele description [Variation Report for NM_014000.3(VCL):c.2828_2829del (p.Pro943fs)]

NM_014000.3(VCL):c.2828_2829del (p.Pro943fs)

Gene:

VCL:vinculin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q22.2

Genomic location:

Preferred name:

NM_014000.3(VCL):c.2828_2829del (p.Pro943fs)

HGVS:

NC_000010.11:g.74111991_74111992del
NG_008868.1:g.118878_118879del
NM_003373.4:c.2746-2193_2746-2192del
NM_014000.3:c.2828_2829delMANE SELECT
NP_054706.1:p.Pro943fs
LRG_383:g.118878_118879del
NC_000010.10:g.75871749_75871750del
NC_000010.10:g.75871749_75871750delCT
NM_014000.2:c.2828_2829delCT
p.(Pro943Argfs*9)
p.P943RfsX9
p.Pro943ArgfsX9

Links:

dbSNP: rs781036800

NCBI 1000 Genomes Browser:

rs781036800

Molecular consequence:

NM_014000.3:c.2828_2829del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003373.4:c.2746-2193_2746-2192del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271292	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Nov 27, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271292

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Nov 27, 2015)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271292.3

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

Description

The p.Pro943fs variant in VCL has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 5/10406 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 781036800). This variant is predicted to cause a frameshift, which alters the pr otein?s amino acid sequence beginning at position 943 and leads to a premature t ermination codon 9 amino acids downstream. Mouse models have shown that loss of function of the VCL gene can lead to DCM (Zemljic-Harpf 2007), although the mode of inheritance associated with such variants in humans is not yet clear. In sum mary, although additional studies are required to fully establish its clinical s ignificance, the p.Pro943fs variant is likely pathogenic.

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

Last Updated: May 1, 2024

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