Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000230215 | SCV000287810 | uncertain significance | Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 | 2018-10-19 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with cysteine at codon 34 of the SDHD protein (p.Phe34Cys). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and cysteine. This variant is present in population databases (rs141802836, ExAC 0.04%). This variant has not been reported in the literature in individuals with SDHD-related disease. ClinVar contains an entry for this variant (Variation ID: 135196). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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 | RCV000569765 | SCV000675108 | likely benign | Hereditary cancer-predisposing syndrome | 2017-09-15 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: In silico models in agreement (benign) |
| ITMI | RCV000122008 | SCV000086219 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |