ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.1594G>T (p.Gly532Cys) (rs779575469)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Klinikum rechts der Isar RCV000995727 SCV001150052 likely pathogenic Alport syndrome, autosomal recessive 2018-03-16 criteria provided, single submitter clinical testing
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV000786944 SCV001427162 pathogenic Alport syndrome 3, autosomal dominant 2018-11-21 criteria provided, single submitter clinical testing A heterozygous missense variant, NM_000091.4(COL4A3):c.1594G>T, has been identified in exon 25 of 52 of the COL4A3 gene. The variant is predicted to result in a major amino acid change from glycine to cysteine at position 532 of the protein (NP_000082.2(COL4A3):p.(Gly532Cys)). The glycine at this position has very high conservation (100 vertebrates, UCSC), and is located within the triple helix essential domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). However, heterozygotes of three different variants in the same codon resulting in a change to serine (0.0008%), arginine (0.0004%) and aspartic acid (0.0008%) have been found in the population. The variant has been previously described as pathogenic and segregated with disease in at least one family with hematuria (Wang, Y.Y. et al., 2004). In addition, p.(Gly532Cys) has been reported heterozygous in an Alport Syndrome patient (Weber, S. et al., 2016). A different variant in the same codon resulting in a change to aspartic acid has also been shown to cause autosomal recessive Alport syndrome (Nagel, M. et al. 2005). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000786944 SCV000925848 pathogenic Alport syndrome 3, autosomal dominant 2019-02-08 no assertion criteria provided clinical testing

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