ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.4495G>T (p.Val1499Leu) (rs527433112)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196985 SCV000249948 likely benign not specified 2014-04-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000617500 SCV000738730 uncertain significance Cardiovascular phenotype 2017-03-14 criteria provided, single submitter clinical testing In silico models in agreement (benign);Insufficient evidence
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000680511 SCV000807896 likely benign Connective tissue disease 2018-06-01 criteria provided, single submitter clinical testing
Invitae RCV000690951 SCV000818682 uncertain significance Ehlers-Danlos syndrome, classic type 2019-08-20 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 1499 of the COL5A2 protein (p.Val1499Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs527433112, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213087). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001137056 SCV001296950 likely benign Ehlers-Danlos syndrome classic type 2 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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