Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001658818 | SCV001873956 | uncertain significance | not provided | 2021-07-07 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 27535533) |
Labcorp Genetics |
RCV003633592 | SCV004540168 | uncertain significance | Ehlers-Danlos syndrome, type 4 | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1136 of the COL3A1 protein (p.Ala1136Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1254636). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL3A1 protein function with a negative predictive value of 95%. 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. |