ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.5048G>A (p.Cys1683Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1386495377
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669331 SCV000794075 uncertain significance Autosomal recessive Alport syndrome 2017-09-08 criteria provided, single submitter clinical testing
Invitae RCV001861775 SCV002288671 likely pathogenic not provided 2022-12-02 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1683 of the COL4A4 protein (p.Cys1683Tyr). This missense change has been observed in individuals with clinical features of autosomal dominant Alport syndrome (PMID: 26809805; Invitae). 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. 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. ClinVar contains an entry for this variant (Variation ID: 553809).
GeneDx RCV001861775 SCV003932980 uncertain significance not provided 2023-06-13 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26809805, 36100708)

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