ClinVar Miner

Submissions for variant NM_014000.3(VCL):c.2852C>G (p.Pro951Arg)

gnomAD frequency: 0.00001  dbSNP: rs368570586
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038818 SCV000062496 likely benign not specified 2010-11-16 criteria provided, single submitter clinical testing Pro951Arg in exon 19 of VCL: The Pro951Arg variant has not been reported in the literature and has not been identified in over 500 Caucasian chromosomes tested by our laboratory. In addition, proline (Pro) at position 951 is highly conserve d across evolutionary distant species, suggesting that a change at this position may not be tolerated. However, this variant was observed to not segregate with disease in one family (one affected individual was negative). Although this cou ld be caused by a second, undetected variant in this family it is more likely th at the Pro951Arg variant is insufficient to cause disease in isolation.
GeneDx RCV000766998 SCV000236477 uncertain significance not provided 2023-03-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001246144 SCV001419484 uncertain significance Dilated cardiomyopathy 1W 2022-10-04 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 951 of the VCL protein (p.Pro951Arg). This variant is present in population databases (rs368570586, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with VCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 45601). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV003372608 SCV004062421 uncertain significance Cardiovascular phenotype 2023-09-20 criteria provided, single submitter clinical testing The p.P951R variant (also known as c.2852C>G), located in coding exon 19 of the VCL gene, results from a C to G substitution at nucleotide position 2852. The proline at codon 951 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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