Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001315071 | SCV001505627 | uncertain significance | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 801 of the COL4A4 protein (p.Gly801Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of COL4A4-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 992405). 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 expected to disrupt COL4A4 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. |
Gene |
RCV001315071 | SCV004014191 | pathogenic | not provided | 2023-07-11 | criteria provided, single submitter | clinical testing | Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD, Jais et al., 2000); Not observed in large population cohorts (gnomAD); In addition, in silico splice predictors suggest this variant may lead to abnormal gene splicing; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24077912, 10752524) |
Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001280847 | SCV001468191 | likely pathogenic | Autosomal recessive Alport syndrome | 2020-06-26 | no assertion criteria provided | clinical testing |