ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.4715C>T (p.Pro1572Leu) (rs121912863)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825912 SCV000967397 uncertain significance not specified 2019-03-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001140736 SCV001301022 uncertain significance Alport syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001245590 SCV001418888 uncertain significance not provided 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1572 of the COL4A4 protein (p.Pro1572Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs121912863, ExAC 0.06%). This variant has been observed in individual(s) with clinical features of Alport syndrome (PMID: 22887978). ClinVar contains an entry for this variant (Variation ID: 17409). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably damaging"; Align-GVGD: "Class C0"). 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 RCV001245590 SCV001789747 uncertain significance not provided 2021-11-29 criteria provided, single submitter clinical testing Observed with a second variant in a patient with mesangial proliferative nephropathy in published literature (Lin et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31019026, 31589614, 32154576, 25381091, 9792860, 22887978)
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV001140736 SCV002047444 likely pathogenic Alport syndrome criteria provided, single submitter research
OMIM RCV000018952 SCV000039239 pathogenic Alport syndrome, autosomal recessive 1998-11-01 no assertion criteria provided literature only

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