ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.8C>T (p.Ala3Val)

gnomAD frequency: 0.00001  dbSNP: rs142139022
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae 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, 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.
GeneDx 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, Rigshospitalet, Copenhagen University Hospital RCV002465536 SCV002760401 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148872 SCV000190616 uncertain significance Pheochromocytoma 2014-06-01 no assertion criteria provided research

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