ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.3691G>A (p.Gly1231Ser)

gnomAD frequency: 0.00002  dbSNP: rs761518401
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670065 SCV000794878 uncertain significance Autosomal recessive Alport syndrome 2017-10-18 criteria provided, single submitter clinical testing
GeneDx RCV001766446 SCV001989053 uncertain significance not provided 2020-02-06 criteria provided, single submitter clinical testing Reported with a mosaic COL4A5 variant in a patient with Alport syndrome in published literature; this variant was present in the patient's unaffected father and sister (Yokota et al., 2016); 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: 27796712, 31312776, 33229591)
Fulgent Genetics, Fulgent Genetics RCV002507169 SCV002816925 uncertain significance Autosomal dominant Alport syndrome; Autosomal recessive Alport syndrome; Benign familial hematuria 2022-04-20 criteria provided, single submitter clinical testing
Invitae RCV001766446 SCV003522314 uncertain significance not provided 2022-02-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1231 of the COL4A3 protein (p.Gly1231Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Alport syndrome (PMID: 27796712). ClinVar contains an entry for this variant (Variation ID: 554433). 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 COL4A3 protein function. 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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