Submissions for variant NM_014000.3(VCL):c.3066C>T (p.Ile1022=)

gnomAD frequency: 0.00009  dbSNP: rs138619320

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038821	SCV000062499	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	Ile1022Ile in exon 20 of VCL: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, and is not located wit hin the splice consensus sequence. It has been identified in 1/3738 African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs138619320). Ile1022Ile in exon 20 of VCL (rs138619320; allele frequency= 1/3738) **
Invitae	RCV000527859	SCV000645864	likely benign	Dilated cardiomyopathy 1W	2023-12-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001697032	SCV000721718	likely benign	not provided	2021-06-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000527859	SCV001263889	uncertain significance	Dilated cardiomyopathy 1W	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000038821	SCV002511793	benign	not specified	2022-04-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002444488	SCV002753837	likely benign	Cardiovascular phenotype	2018-12-31	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003964864	SCV004783233	likely benign	VCL-related condition	2020-05-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).