ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.3913G>A (p.Ala1305Thr) (rs372897632)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621235 SCV000738427 uncertain significance Cardiovascular phenotype 2016-03-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)
Invitae RCV000233551 SCV000284817 uncertain significance Ehlers-Danlos syndrome, classic type 2016-03-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1305 of the COL5A2 protein (p.Ala1305Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs372897632, ExAC 0.02%) but has not been reported in the literature in individuals with a COL5A2-related disease. 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. In summary, this variant is a rare missense change that is not predicted to affect protein function or cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
