ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.1844C>T (p.Ala615Val) (rs148669762)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000701609 SCV000830419 uncertain significance Dilated cardiomyopathy 1W 2018-11-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 615 of the VCL protein (p.Ala615Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs148669762, ExAC 0.005%). This variant has been observed in an individual affected with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 45593). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038809 SCV000062487 uncertain significance not specified 2012-06-07 criteria provided, single submitter clinical testing The Ala615Val variant in VCL has not been reported in the literature nor previou sly identified by our laboratory. This variant was identified in 1/7020 European American chromosomes from a broad population by the NHLBI Exome Sequencing Proj ect (http://evs.gs.washington.edu/EVS/; dbSNP rs148669762). However, this could represent a presymptomatic individual in the general population. Computational a nalyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional information is required to fully establish the pathogeni city of this variant.

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