Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001217421 | SCV001389259 | uncertain significance | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2022-06-23 | criteria provided, single submitter | clinical testing | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 946537). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1571 of the COL12A1 protein (p.Asp1571Glu). |
Prevention |
RCV003405402 | SCV004116162 | uncertain significance | COL12A1-related condition | 2022-11-14 | criteria provided, single submitter | clinical testing | The COL12A1 c.4713T>A variant is predicted to result in the amino acid substitution p.Asp1571Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-75853082-A-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV003442777 | SCV004169606 | uncertain significance | not provided | 2023-05-19 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function |