ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.2000C>T (p.Thr667Met)

gnomAD frequency: 0.00008  dbSNP: rs143090687
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001054370 SCV001218680 uncertain significance not provided 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 667 of the PCDH15 protein (p.Thr667Met). This variant is present in population databases (rs143090687, gnomAD 0.03%). 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: 850242). 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.
Fulgent Genetics, Fulgent Genetics RCV002479330 SCV002780963 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2021-07-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV004031712 SCV004998821 uncertain significance Inborn genetic diseases 2023-12-21 criteria provided, single submitter clinical testing The c.2000C>T (p.T667M) alteration is located in exon 17 (coding exon 16) of the PCDH15 gene. This alteration results from a C to T substitution at nucleotide position 2000, causing the threonine (T) at amino acid position 667 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV001054370 SCV005078868 uncertain significance not provided 2024-01-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001274798 SCV001459225 uncertain significance Usher syndrome type 1F 2020-09-16 no assertion criteria provided clinical testing

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