ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.2417dup (p.Gly807fs)

dbSNP: rs1440033157
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667462 SCV000791913 likely pathogenic Autosomal recessive Alport syndrome 2017-05-31 criteria provided, single submitter clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000667462 SCV001150054 pathogenic Autosomal recessive Alport syndrome 2019-06-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000667462 SCV001983759 likely pathogenic Autosomal recessive Alport syndrome 2021-09-29 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.2417dupC (p.Gly807ArgfsX28) 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 allele was found at a frequency of 5.8e-06 in 172936 control chromosomes. c.2417dupC has been reported in the literature in at least one individual affected with Alport Syndrome, Autosomal Recessive (Heidet_2001). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV003148822 SCV003837027 pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11134255)
Invitae RCV003148822 SCV004294022 pathogenic not provided 2023-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly807Argfs*28) in the COL4A3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265, 26809805, 27281700). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alport syndrome (PMID: 11134255). ClinVar contains an entry for this variant (Variation ID: 552236). For these reasons, this variant has been classified as Pathogenic.

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