Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Molecular Genetics, |
RCV005250415 | SCV005900302 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2025-02-06 | criteria provided, single submitter | clinical testing | This sequence change in DSP is predicted to replace asparagine with serine at codon 2234, p.(Asn2234Ser). The asparagine residue is highly conserved (100 vertebrates, Multiz Alignments) and is not located in an annotated domain. There is a small physicochemical difference between asparagine and serine. The highest population minor allele frequency in the population database gnomAD v4.1 is 0.00008% (1/1,180,050 alleles) in the European (non-Finnish) population. To our knowledge, this variant is novel and has not been previously reported in the relevant scientific literature or databases. Computational evidence predicts a benign effect for the missense substitution (REVEL = 0.066). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.7.1, this variant is classified as VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, BP4. |
| Ambry Genetics | RCV005326077 | SCV005995657 | likely benign | Cardiovascular phenotype | 2025-02-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |