ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.391G>T (p.Glu131Ter)

gnomAD frequency: 0.00002  dbSNP: rs1346138010
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674775 SCV000800170 likely pathogenic Autosomal recessive Alport syndrome 2018-05-23 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763077 SCV000893589 pathogenic Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000674775 SCV001372411 pathogenic Autosomal recessive Alport syndrome 2020-06-03 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.391G>T (p.Glu131X) 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 8e-06 in 249198 control chromosomes (gnomAD). c.391G>T has been reported in the literature in at least one individual affected with Alport Syndrome, Autosomal Recessive (e.g. Storey_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001218262 SCV001390136 pathogenic not provided 2023-05-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 558496). This premature translational stop signal has been observed in individual(s) with clinical features of Alport syndrome (PMID: 24052634). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu131*) 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).
Natera, Inc. RCV001830467 SCV002076379 pathogenic Alport syndrome 2020-05-04 no assertion criteria provided clinical testing

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