ClinVar Miner

Submissions for variant NM_014000.3(VCL):c.2923C>T (p.Arg975Trp)

gnomAD frequency: 0.00001  dbSNP: rs121917776
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620759 SCV000735453 uncertain significance Cardiovascular phenotype 2024-05-07 criteria provided, single submitter clinical testing The p.R975W variant (also known as c.2923C>T), located in coding exon 19 of the VCL gene, results from a C to T substitution at nucleotide position 2923. The arginine at codon 975 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000012980 SCV001204022 uncertain significance Dilated cardiomyopathy 1W 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 975 of the VCL protein (p.Arg975Trp). This variant is present in population databases (rs121917776, gnomAD 0.03%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) (PMID: 11815424, 17097056). ClinVar contains an entry for this variant (Variation ID: 12197). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects VCL function (PMID: 23159629, 27503891). 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.
Fulgent Genetics, Fulgent Genetics RCV002482857 SCV002800860 uncertain significance Dilated cardiomyopathy 1W; Hypertrophic cardiomyopathy 15 2021-10-28 criteria provided, single submitter clinical testing
OMIM RCV000012980 SCV000033225 pathogenic Dilated cardiomyopathy 1W 2006-10-20 no assertion criteria provided literature only
OMIM RCV000012981 SCV000033226 pathogenic Hypertrophic cardiomyopathy 15 2006-10-20 no assertion criteria provided literature only

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