ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.4892C>T (p.Thr1631Met) (rs764446683)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198222 SCV000249920 uncertain significance not provided 2017-11-07 criteria provided, single submitter clinical testing The T1631M variant of uncertain significance in the COL5A1 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 0.003%-0.004% alleles across ethnic groups in large population cohorts (Lek et al., 2016). The T1631M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.Thus, additional evidence is needed to determine whether this variant is pathogenic or benign.
Invitae RCV000703884 SCV000832809 uncertain significance Ehlers-Danlos syndrome, classic type 2018-04-04 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1631 of the COL5A1 protein (p.Thr1631Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs764446683, ExAC 0.01%). This variant has not been reported in the literature in individuals with COL5A1-related disease. ClinVar contains an entry for this variant (Variation ID: 213061). 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: "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.
Mendelics RCV000703884 SCV001137952 uncertain significance Ehlers-Danlos syndrome, classic type 2019-05-28 criteria provided, single submitter clinical testing

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