ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.4522G>A (p.Gly1508Ser)

gnomAD frequency: 0.00001  dbSNP: rs1003748020
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001862424 SCV002254318 likely pathogenic not provided 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1508 of the COL4A4 protein (p.Gly1508Ser). This variant also falls at the last nucleotide of exon 46, which is part of the consensus splice site for this exon. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of Alport syndrome (PMID: 24052634; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 829920). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001029868 SCV001192656 pathogenic Autosomal dominant Alport syndrome 2019-11-19 no assertion criteria provided clinical testing
Center for Computational Biology & Bioinformatics, University of California, San Diego RCV004570083 SCV005049936 uncertain significance Meniere disease 2024-06-03 no assertion criteria provided research

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