ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.4663G>A (p.Ala1555Thr)

gnomAD frequency: 0.00001  dbSNP: rs774089446
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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 RCV001366658 SCV001562969 uncertain significance not provided 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1555 of the COL4A3 protein (p.Ala1555Thr). This variant is present in population databases (rs774089446, gnomAD 0.02%). This missense change has been observed in individual(s) with Alport syndrome (internal data). ClinVar contains an entry for this variant (Variation ID: 1057636). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Ala1555 amino acid residue in COL4A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31328266). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
GeneDx RCV001366658 SCV005369097 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001826050 SCV002076435 uncertain significance Alport syndrome 2020-01-24 no assertion criteria provided clinical testing

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