Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825908 | SCV000967393 | uncertain significance | not specified | 2018-08-07 | criteria provided, single submitter | clinical testing | The p.His1471Gln variant in COL4A4 has not been previously reported in individua ls with hearing loss or Alport syndrome but has been identified in 0.01% (4/3357 2) Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad. broadinstitute.org). Computational prediction tools and conservation analysis su ggest that the p.His1471Gln variant may impact the protein, though this informat ion is not predictive enough to determine pathogenicity. In summary, the clinica l significance of the p.His1471Gln variant is uncertain. ACMG/AMP Criteria appli ed: PP3, PM2_Supporting. |
Invitae | RCV001313936 | SCV001504447 | uncertain significance | not provided | 2022-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1471 of the COL4A4 protein (p.His1471Gln). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL4A4-related conditions. ClinVar contains an entry for this variant (Variation ID: 667224). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 |
RCV001313936 | SCV002765313 | uncertain significance | not provided | 2022-06-16 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002478937 | SCV002784392 | uncertain significance | Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-05-31 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001275117 | SCV001459916 | uncertain significance | Alport syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |