ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.32G>A (p.Arg11His)

dbSNP: rs767802663
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233939 SCV000287800 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 11 of the SDHC protein (p.Arg11His). This variant is present in population databases (rs767802663, gnomAD 0.003%). This missense change has been observed in individual(s) with a personal and family history of breast and/or ovarian cancer (PMID: 28202063). ClinVar contains an entry for this variant (Variation ID: 239454). 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 histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001762528 SCV001998923 uncertain significance not provided 2024-01-05 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 a personal and/or family history of breast cancer (PMID: 28202063); This variant is associated with the following publications: (PMID: 28202063)
Sema4, Sema4 RCV002256146 SCV002527107 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter curation
Baylor Genetics RCV004567729 SCV005056666 uncertain significance Gastrointestinal stromal tumor 2023-12-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002256146 SCV005161233 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-28 criteria provided, single submitter clinical testing The p.R11H variant (also known as c.32G>A), located in coding exon 2 of the SDHC gene, results from a G to A substitution at nucleotide position 32. The arginine at codon 11 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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