ClinVar Miner

Submissions for variant NM_000091.4(COL4A3):c.1354G>A (p.Gly452Arg) (rs772958162)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666502 SCV000790807 likely pathogenic Alport syndrome, autosomal recessive 2017-04-10 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198699 SCV001369694 uncertain significance Alport syndrome 3, autosomal dominant 2019-10-02 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PP5,PP3,PM2.
Invitae RCV000681919 SCV001399187 pathogenic not provided 2019-08-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 452 of the COL4A3 protein (p.Gly452Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of Alport Syndrome (PMID: 24633401, 24854265, 24033287). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID:551440). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Gharavi Laboratory,Columbia University RCV000681919 SCV000809402 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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