ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.2696G>A (p.Gly899Glu) (rs201382636)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541053 SCV000656139 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2017-04-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 899 of the COL12A1 protein (p.Gly899Glu). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs201382636, ExAC 0.006%) but has not been reported in the literature in individuals with a COL12A1-related disease. 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").  This variant occurs outside of the conserved triple-helical domain of the collagen protein where amino acid substitutions are rarely pathogenic. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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