Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000471140 | SCV000546042 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3 of the SDHC protein (p.Ala3Val). This variant is present in population databases (rs142139022, gnomAD 0.004%). This missense change has been observed in individual(s) with sporadic pheochromocytoma (PMID: 22517554). ClinVar contains an entry for this variant (Variation ID: 161387). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV000563869 | SCV000675101 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | The p.A3V variant (also known as c.8C>T), located in coding exon 1 of the SDHC gene, results from a C to T substitution at nucleotide position 8. The alanine at codon 3 is replaced by valine, an amino acid with similar properties. This alteration has been reported in a 36-year-old individual with a sporadic pheochromocytoma (Lefebvre S et al. Horm. Metab. Res. 2012 May;44:334-8). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV002464125 | SCV002758993 | uncertain significance | not provided | 2022-11-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with pheochromocytoma (Lefebvre et al., 2012); This variant is associated with the following publications: (PMID: 25637381, 31854063, 22517554) |
| Center for Genomic Medicine, |
RCV002465536 | SCV002760401 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003998177 | SCV004833745 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-10-06 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with valine at codon 3 of the SDHC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with hereditary pheochromocytoma (PMID: 22517554). This variant has been identified in 5/251188 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV004567168 | SCV005056657 | uncertain significance | Gastrointestinal stromal tumor | 2024-02-28 | criteria provided, single submitter | clinical testing | |
| CSER _CC_NCGL, |
RCV000148872 | SCV000190616 | uncertain significance | Pheochromocytoma | 2014-06-01 | no assertion criteria provided | research |