ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.2906C>G (rs35138315)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522361 SCV000617815 pathogenic not provided 2017-06-28 criteria provided, single submitter clinical testing The S969X variant in the COL4A4 gene has been reported previously, in the compound heterozygous and homozygous states, in individuals with Alport's disease (Dagher et al., 2002; Storey et al., 2013). In at least two families with autosomal recessive Alport's disease, heterozygous carriers of S969X were noted to have hematuria (Dagher et al., 2002). The S969X variant was also detected in the heterozygous state in an individual with focal segmental glomerulosclerosis (Gast et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The S969X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret S969X as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000763076 SCV000893587 pathogenic Alport syndrome, autosomal recessive 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000522361 SCV001228460 pathogenic not provided 2019-11-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser969*) in the COL4A4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs35138315, ExAC 0.01%). This variant has been observed in individuals affected with Alport syndrome (PMID: 12325029, 24052634). ClinVar contains an entry for this variant (Variation ID: 449549). Loss-of-function variants in COL4A4 are known to be pathogenic (PMID: 11961012, 14582039, 19129241, 21196518, 24052634, 24522496, 24854265, 25307543, 26809805, 27281700). For these reasons, this variant has been classified as Pathogenic.
Cavalleri Lab, Royal College of Surgeons in Ireland RCV000763076 SCV001305529 pathogenic Alport syndrome, autosomal recessive 2020-05-27 criteria provided, single submitter research
Cavalleri Lab, Royal College of Surgeons in Ireland RCV001171331 SCV001328278 pathogenic Chronic kidney disease 2020-05-28 criteria provided, single submitter research PVS1, PS1
Counsyl RCV000763076 SCV001132367 pathogenic Alport syndrome, autosomal recessive 2016-11-18 no assertion criteria provided clinical testing

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