Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002228410 | SCV000287810 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 34 of the SDHD protein (p.Phe34Cys). This variant is present in population databases (rs141802836, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SDHD-related conditions. ClinVar contains an entry for this variant (Variation ID: 135196). 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 with a negative predictive value of 95%. 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 | RCV000569765 | SCV000675108 | likely benign | Hereditary cancer-predisposing syndrome | 2017-09-15 | 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. |
Gene |
RCV001545828 | SCV001765234 | uncertain significance | not provided | 2023-11-13 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in at least one individual with a personal history of pheochromocytoma and/or paraganglioma (PMID: 34906457); This variant is associated with the following publications: (PMID: 24728327, 34906457) |
St. |
RCV003230259 | SCV003928129 | uncertain significance | Paragangliomas 1 | 2023-04-24 | criteria provided, single submitter | clinical testing | The SDHD c.101T>G (p.Phe34Cys) missense change has a maximum subpopulation frequency of 0.036% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with SDHD-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
ITMI | RCV000122008 | SCV000086219 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |