ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.2192A>C (p.Glu731Ala)

dbSNP: rs749438162
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520870 SCV000621547 uncertain significance not provided 2017-10-09 criteria provided, single submitter clinical testing The E731A variant in the PCDH15 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E731A variant is not observed in large population cohorts (Lek et al., 2016). The E731A variant is a non-conservative amino acid substitution, which occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret E731A as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000520870 SCV003788221 uncertain significance not provided 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 731 of the PCDH15 protein (p.Glu731Ala). 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: 452717). 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: "Possibly 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.
Ambry Genetics RCV004023618 SCV004998823 uncertain significance Inborn genetic diseases 2023-10-05 criteria provided, single submitter clinical testing The c.2192A>C (p.E731A) alteration is located in exon 18 (coding exon 17) of the PCDH15 gene. This alteration results from a A to C substitution at nucleotide position 2192, causing the glutamic acid (E) at amino acid position 731 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001829528 SCV002088499 uncertain significance Usher syndrome type 1F 2020-02-26 no assertion criteria provided clinical testing

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