ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.734G>A (p.Arg245Gln)

gnomAD frequency: 0.00005  dbSNP: rs562377533
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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, Mass General Brigham Personalized Medicine RCV000151640 SCV000199875 uncertain significance not specified 2013-06-12 criteria provided, single submitter clinical testing The Arg245Gln variant in PCDH15 has not been reported in individuals with hearin g loss and was not identified in large population studies. Computational analyse s (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SI FT) do not provide strong support for or against an impact to the protein. In s ummary, additional studies are needed to fully assess the clinical significance of the Arg245Gln variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001314166 SCV001504690 uncertain significance not provided 2025-01-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 245 of the PCDH15 protein (p.Arg245Gln). This variant is present in population databases (rs562377533, gnomAD 0.02%). 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: 164932). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PCDH15 protein function with a negative predictive value of 95%. 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 RCV002492560 SCV002800188 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2021-09-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV001835690 SCV002094261 uncertain significance Usher syndrome type 1F 2020-02-11 no assertion criteria provided clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004815218 SCV005069463 uncertain significance Optic atrophy 2023-01-01 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004734708 SCV005367471 uncertain significance PCDH15-related disorder 2024-09-12 no assertion criteria provided clinical testing The PCDH15 c.734G>A variant is predicted to result in the amino acid substitution p.Arg245Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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