ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.4420_4424del (p.Leu1474fs) (rs1445615417)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671970 SCV000797017 pathogenic Alport syndrome, autosomal recessive 2018-01-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000671970 SCV001442629 pathogenic Alport syndrome, autosomal recessive 2020-10-12 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.4420_4424delCTTTT (p.Leu1474CysfsX34) 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. The variant was absent in 249424 control chromosomes (gnomAD). c.4420_4424delCTTTT has been reported in the literature in individuals affected with Alport Syndrome, Autosomal Recessive (Mochizuki_1994, Moriniere_2014). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001381660 SCV001580149 pathogenic not provided 2020-09-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1474Cysfs*34) 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 individual(s) with autosomal dominant and autosomal recessive Alport syndrome (PMID: 7987396, 7987301). It is also known as a 5bp CTTTT deletion in the literature. ClinVar contains an entry for this variant (Variation ID: 556032). Loss-of-function variants in COL4A3 are known to be pathogenic (PMID: 8956999, 24854265). For these reasons, this variant has been classified as Pathogenic.

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