Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523311 | SCV000620532 | uncertain significance | not provided | 2017-08-31 | criteria provided, single submitter | clinical testing | The L1564S variant in the COL12A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L1564S 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. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on currently available evidence, we interpret L1564S as a variant of uncertain significance. |
Invitae | RCV000811756 | SCV000952039 | uncertain significance | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2018-12-30 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 1564 of the COL12A1 protein (p.Leu1564Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451784). |