Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000555154 | SCV000641430 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-07-25 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 465965). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. This variant is present in population databases (rs746666691, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 8 of the SDHC protein (p.His8Tyr). |
| Ambry Genetics | RCV003302832 | SCV003993195 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The p.H8Y variant (also known as c.22C>T), located in coding exon 2 of the SDHC gene, results from a C to T substitution at nucleotide position 22. The histidine at codon 8 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |