ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.1427G>A (p.Arg476Gln)

gnomAD frequency: 0.00006  dbSNP: rs376673751
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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 RCV000517537 SCV000612930 uncertain significance not specified 2016-09-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002476038 SCV002780437 uncertain significance Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome; Brain small vessel disease 1 with or without ocular anomalies; Hemorrhage, intracerebral, susceptibility to; Retinal arterial tortuosity; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 2021-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002525031 SCV003733953 uncertain significance Inborn genetic diseases 2022-12-29 criteria provided, single submitter clinical testing The c.1427G>A (p.R476Q) alteration is located in exon 23 (coding exon 23) of the COL4A1 gene. This alteration results from a G to A substitution at nucleotide position 1427, causing the arginine (R) at amino acid position 476 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003546569 SCV004270722 uncertain significance not provided 2024-09-05 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 476 of the COL4A1 protein (p.Arg476Gln). This variant is present in population databases (rs376673751, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 447158). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL4A1 protein function with a negative predictive value of 95%. 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.

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