Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000200680 | SCV000249858 | uncertain significance | not provided | 2018-10-19 | criteria provided, single submitter | clinical testing | p.Val1799Ile (V1799I) GTT>ATT: c.5395 G>A in exon 66 of the COL5A1 gene (NM_000093.3) The V1799I variant has not been published as a mutation or reported as a benign polymorphism to our knowledge. The V1799I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1799I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, and this substitution occurs at a position that is not conserved. Furthermore, the V1799I variant is located in the C-terminal propeptide, not in the triple helical region of the COL5A1 gene where the majority of missense mutations occur (Symoens S et al., 2012). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Moreover, no missense mutations in nearby residues have been reported in association with EDS, indicating this region of the protein may be tolerant of change.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.This variant was found in TAADV2-PANCARD |