ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.4367T>C (p.Ile1456Thr)

dbSNP: rs2076749331
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812926 SCV001472489 uncertain significance not provided 2019-12-15 criteria provided, single submitter clinical testing The PCDH15 c.4367T>C; p.Ile1456Thr variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is also absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The isoleucine at codon 1456 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Ile1456Thr variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001812926 SCV002271604 uncertain significance not provided 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1456 of the PCDH15 protein (p.Ile1456Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 993842). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Natera, Inc. RCV001830086 SCV002091672 uncertain significance Usher syndrome type 1F 2020-11-17 no assertion criteria provided clinical testing

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