ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.2510G>C (p.Gly837Ala)

gnomAD frequency: 0.00001  dbSNP: rs201648982
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669439 SCV000794190 likely pathogenic Autosomal recessive Alport syndrome 2017-09-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855519 SCV002228705 pathogenic not provided 2023-06-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) performed at Invitae indicates that this missense variant is expected to disrupt COL4A4 protein function. ClinVar contains an entry for this variant (Variation ID: 553903). This missense change has been observed in individuals with Alport syndrome (PMID: 24633401, 27281700, 31677115). This variant is present in population databases (rs201648982, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 837 of the COL4A4 protein (p.Gly837Ala).
3billion RCV000669439 SCV004013586 likely pathogenic Autosomal recessive Alport syndrome criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.97; 3Cnet: 0.36). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000553903 / PMID: 24633401). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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