ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.446C>T (p.Pro149Leu) (rs369971694)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621418 SCV000738632 uncertain significance Cardiovascular phenotype 2016-12-22 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000804672 SCV000944590 uncertain significance Ehlers-Danlos syndrome, classic type 2019-02-04 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 149 of the COL5A1 protein (p.Pro149Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs369971694, ExAC 0.03%). This variant has not been reported in the literature in individuals with COL5A1-related disease. ClinVar contains an entry for this variant (Variation ID: 519635). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 RCV000804672 SCV001329745 likely benign Ehlers-Danlos syndrome, classic type 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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