ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.4413C>G (p.His1471Gln)

gnomAD frequency: 0.00001  dbSNP: rs1478610555
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
GeneDx 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, Fulgent Genetics RCV002478937 SCV002784392 uncertain significance Autosomal recessive Alport syndrome; Benign familial hematuria 2022-05-31 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275117 SCV001459916 uncertain significance Alport syndrome 2020-09-16 no assertion criteria provided clinical testing

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