ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.476G>A (p.Gly159Asp)

dbSNP: rs2147759208
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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 RCV001362323 SCV001558334 uncertain significance not provided 2020-08-19 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 COL4A5 protein function. This variant has been observed in individual(s) with clinical features of Alport syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 159 of the COL4A5 protein (p.Gly159Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
Precision Medicine Center, Zhengzhou University RCV001391160 SCV001593056 likely pathogenic X-linked Alport syndrome criteria provided, single submitter research PM1:Located in a mutational hot spot PM2:not found in gnomAD PP1:Cosegregation with disease in multiple affected family members PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product PP4:Patient's phenotype is highly specific for a disease
3billion RCV001391160 SCV003842148 uncertain significance X-linked Alport syndrome 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 0.66). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL4A5 related disorder (ClinVar ID: VCV001053912). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.

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