ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.2371C>T (rs1060499654)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva,University Hospital of Geneva RCV000449569 SCV000537702 likely pathogenic Alport syndrome, autosomal recessive 2016-07-11 criteria provided, single submitter clinical testing This heterozygous non-sense variant in the COL4A3 gene (autosomal recessive transmission) is present in a male patient with Alport syndrome who also harbours a missense variant in the same gene (see below). The segregation analysis could not be done, but regarding the clinical presentation of the patient, it is assumed that these two variants are present in compound heterozygosity
Counsyl RCV000449569 SCV000797888 pathogenic Alport syndrome, autosomal recessive 2018-02-13 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763472 SCV000894254 pathogenic Alport syndrome 3, autosomal dominant; Alport syndrome, autosomal recessive; Benign familial hematuria 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001213210 SCV001384831 pathogenic not provided 2019-05-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg791*) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with and without another COL4A3 variant in individuals affected with Alport syndrome (PMID: 25307543, 22887978). ClinVar contains an entry for this variant (Variation ID: 397514). Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). For these reasons, this variant has been classified as Pathogenic.
Molecular Biology Laboratory, Fundació Puigvert RCV000449569 SCV001424999 pathogenic Alport syndrome, autosomal recessive 2020-02-01 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000449569 SCV001482249 pathogenic Alport syndrome, autosomal recessive 2021-02-19 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.2371C>T (p.Arg791X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249528 control chromosomes. c.2371C>T has been reported in the literature in individuals affected with Alport Syndrome, Autosomal Recessive (e.g. Zhang_2012, Nabais Sa'_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories cited the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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