ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.3308C>T (p.Pro1103Leu) (rs150401168)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196495 SCV000249979 uncertain significance not provided 2016-10-26 criteria provided, single submitter clinical testing The P1103L variant in the COL5A2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The P1103L variant is a semi-conservative amino acid substitution as these residues share similar properties, but differ in size, charge, or other properties which may impact secondary structure. The P1103 residue is mostly conserved across mammals. In silico analysis was inconsistent with regard to the effect this variant may have on the protein structure/function. The P1103L variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Nevertheless, no other disease-causing mutations have been reported in surrounding residues of the COL5A2 protein, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if P1103L is a disease-causing mutation or a rare benign variant.
Invitae RCV000799741 SCV000939417 uncertain significance Ehlers-Danlos syndrome, classic type 2018-10-02 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1103 of the COL5A2 protein (p.Pro1103Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs150401168, ExAC 0.01%). This variant has not been reported in the literature in individuals with COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213116). 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 C25"). 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.

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