Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240532 | SCV001231428 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2023-09-28 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 31 of the SDHD protein (p.Ile31Val). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHD protein function. ClinVar contains an entry for this variant (Variation ID: 860158). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. This variant is not present in population databases (gnomAD no frequency). |
| Ambry Genetics | RCV002374977 | SCV002688111 | likely benign | Hereditary cancer-predisposing syndrome | 2021-01-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
| Genetic Services Laboratory, |
RCV003151276 | SCV003840034 | uncertain significance | not specified | 2022-08-08 | no assertion criteria provided | clinical testing | DNA sequence analysis of the SDHD gene demonstrated a sequence change, c.91A>G, in exon 2 that results in an amino acid change, p.Ile31Val. This sequence change does not appear to have been previously described in individuals with SDHD-related disorders and has also not been described in population databases such as ExAC and gnomAD. The p.Ile31Val change affects a poorly conserved amino acid residue located in a domain of the SDHD protein that is not known to be functional. The p.Ile31Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ile31Val change remains unknown at this time. |