Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001307614 | SCV001497033 | uncertain significance | Hypertrophic cardiomyopathy | 2020-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with cysteine at codon 412 of the JPH2 protein (p.Ser412Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with JPH2-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV004034131 | SCV003530723 | uncertain significance | Cardiovascular phenotype | 2021-08-17 | criteria provided, single submitter | clinical testing | The c.1235C>G (p.S412C) alteration is located in exon 3 (coding exon 3) of the JPH2 gene. This alteration results from a C to G substitution at nucleotide position 1235, causing the serine (S) at amino acid position 412 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |