ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.242G>T (p.Gly81Val)

gnomAD frequency: 0.00001  dbSNP: rs781756162
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015507 SCV001176349 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-20 criteria provided, single submitter clinical testing The p.G81V variant (also known as c.242G>T) is located in coding exon 5 of the SDHC gene. The glycine at codon 81 is replaced by valine, an amino acid with dissimilar properties. This alteration was identified in 1/143 Danish patients with pheochromocytoma and/or paraganglioma. (Bennedbæk M et al. Hered Cancer Clin Pract. 2016 Jun;14:13). This change occurs in the first base pair of coding exon 5. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860795 SCV002302503 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2022-01-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 821264). This missense change has been observed in individual(s) with paraganglioma-pheochromocytoma syndrome (PMID: 27279923). This variant is present in population databases (rs781756162, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 81 of the SDHC protein (p.Gly81Val). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
GeneDx RCV004588472 SCV005080150 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27279923)

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