ClinVar Miner

Submissions for variant NM_000091.4(COL4A3):c.1483C>T (p.His495Tyr) (rs200510532)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000259762 SCV000428164 uncertain significance Alport syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000519515 SCV000618077 uncertain significance not provided 2018-07-25 criteria provided, single submitter clinical testing The H495Y variant in the COL4A3 gene has been reported previously in association with COL4A3-related disorders (Weber et al., 2016). The variant is observed in 18/10,150 (0.177%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). H495Y is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in silico analyses, which includes protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret H495Y as a variant of uncertain significance.
Athena Diagnostics Inc RCV000519515 SCV001143218 uncertain significance not provided 2019-07-17 criteria provided, single submitter clinical testing

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