ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.3638C>T (p.Pro1213Leu) (rs1056466895)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796616 SCV000936136 uncertain significance Ehlers-Danlos syndrome, classic type 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1213 of the COL5A2 protein (p.Pro1213Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL5A2-related disease. 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: "Not available"; 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000700 SCV001157739 uncertain significance Ehlers-Danlos syndrome classic type 2 2018-07-25 criteria provided, single submitter clinical testing The COL5A2 c.3638C>T; p.Pro1213Leu variant (rs1056466895), to our knowledge, has not been described in the medical literature or in gene-specific databases, and is only observed on 2 alleles in the Genome Aggregation Database. The proline at codon 1213 is highly conserved, but computational algorithms (PolyPhen-2: probably damaging, SIFT: tolerated) predict conflicting effects of this variant on protein structure/function. Due to lack of clinical and functional information regarding this variant, its clinical significance cannot be determined with certainty.

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