ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.1396G>A (p.Gly466Arg)

gnomAD frequency: 0.00002  dbSNP: rs201859109
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000518015 SCV000612959 pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481668 SCV002788888 pathogenic Autosomal recessive Alport syndrome; Benign familial hematuria 2021-07-20 criteria provided, single submitter clinical testing
Invitae RCV000518015 SCV003524981 likely pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 466 of the COL4A4 protein (p.Gly466Arg). This variant is present in population databases (rs201859109, gnomAD 0.007%). This missense change has been observed in individuals with autosomal dominant COL4A4-related conditions (PMID: 26809805, 29801666; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 447180). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL4A4 protein function. 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.
Counsyl RCV000984248 SCV001132368 uncertain significance Autosomal recessive Alport syndrome 2019-01-24 no assertion criteria provided clinical testing

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