Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000600771 | SCV000732033 | likely benign | not specified | 2017-12-21 | criteria provided, single submitter | clinical testing | p.Asp1193Asn in exon 42 of COL4A3: This variant is not expected to have clinical significance because the aspartic acid (Asp) at position 1193 is not conserved in mammals or evolutionarily distant species and 4 mammals (shrew, wallaby, opos sum, and Tasmanian devil) carry an asparagine (Asn) at this position despite nea rby amino acid sequence conservation. Additional computational prediction tools and conservation analysis suggest that the variant may not impact the protein. This variant been identified in 5/120268 of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; ). ACMG/AMP Crit eria Applied BP4_strong. |
| Gene |
RCV001770545 | SCV001992974 | uncertain significance | not provided | 2024-09-05 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the X 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; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001770545 | SCV005812030 | uncertain significance | not provided | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1193 of the COL4A3 protein (p.Asp1193Asn). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with COL4A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 517651). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |