ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.4316C>T (p.Pro1439Leu)

gnomAD frequency: 0.00004  dbSNP: rs374714898
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000490047 SCV000577391 uncertain significance not provided 2017-03-31 criteria provided, single submitter clinical testing The P1439L variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P1439L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1439L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P1439L as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000490047 SCV003471827 uncertain significance not provided 2021-11-05 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1439 of the PCDH15 protein (p.Pro1439Leu). This variant is present in population databases (rs374714898, gnomAD 0.003%). 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: 426841). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002526033 SCV003759234 uncertain significance Inborn genetic diseases 2021-08-16 criteria provided, single submitter clinical testing The c.4316C>T (p.P1439L) alteration is located in exon 32 (coding exon 31) of the PCDH15 gene. This alteration results from a C to T substitution at nucleotide position 4316, causing the proline (P) at amino acid position 1439 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001272407 SCV001454392 uncertain significance Usher syndrome type 1F 2020-03-17 no assertion criteria provided clinical testing

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