Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000610079 | SCV000711186 | uncertain significance | not specified | 2017-08-03 | criteria provided, single submitter | clinical testing | The p.Phe979Ser variant in PCDH15 has not been previously reported in individual s with hearing loss, but has been identified in 1/33562 Latino chromosomes by th e Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP r s150891423). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predic tion tools and conservation analysis suggest that the variant may impact the pro tein, though this information is not predictive enough to determine pathogenicit y. In summary, the clinical significance of the p.Phe979Ser variant is uncertain . |
Labcorp Genetics |
RCV001071709 | SCV001237027 | uncertain significance | not provided | 2022-05-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 979 of the PCDH15 protein (p.Phe979Ser). This variant is present in population databases (rs150891423, 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: 504667). 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. |
Ambry Genetics | RCV002532732 | SCV003698814 | uncertain significance | Inborn genetic diseases | 2022-09-06 | criteria provided, single submitter | clinical testing | The c.2936T>C (p.F979S) alteration is located in exon 22 (coding exon 21) of the PCDH15 gene. This alteration results from a T to C substitution at nucleotide position 2936, causing the phenylalanine (F) at amino acid position 979 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001829694 | SCV002093079 | uncertain significance | Usher syndrome type 1F | 2019-11-11 | no assertion criteria provided | clinical testing |