ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.8C>T (p.Ala3Val) (rs142139022)

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Total submissions: 3
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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 2020-10-20 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 3 of the SDHC protein (p.Ala3Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs142139022, ExAC 0.01%). This variant has been reported in an individual affected with sporadic pheochromocytoma (PMID: 22517554). ClinVar contains an entry for this variant (Variation ID: 161387). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. 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 2019-12-23 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.
CSER _CC_NCGL, University of Washington RCV000148872 SCV000190616 uncertain significance Pheochromocytoma 2014-06-01 no assertion criteria provided research

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