ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.1295C>T (p.Pro432Leu) (rs534253913)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665542 SCV000789683 uncertain significance Alport syndrome, autosomal recessive 2017-02-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001136570 SCV001296423 uncertain significance Alport syndrome 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001362305 SCV001558316 uncertain significance not provided 2020-02-07 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 432 of the COL4A3 protein (p.Pro432Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs534253913, ExAC 0.03%). This variant has been observed in individual(s) with bilateral sensorineural hearing loss (PMID: 23967202). ClinVar contains an entry for this variant (Variation ID: 550720). 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.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375163 SCV001571721 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PS1_Supporting, PM2_Moderate, PP3_Supporting
Nilou-Genome Lab RCV000665542 SCV001781446 uncertain significance Alport syndrome, autosomal recessive 2021-07-14 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV001280876 SCV001781447 uncertain significance Alport syndrome 3, autosomal dominant 2021-07-14 criteria provided, single submitter clinical testing
GeneDx RCV001362305 SCV001986279 uncertain significance not provided 2020-04-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease; This variant is associated with the following publications: (PMID: 23967202)
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV001280876 SCV001468221 likely pathogenic Alport syndrome 3, autosomal dominant 2020-02-07 no assertion criteria provided clinical testing

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