ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.259A>C (p.Met87Leu)

gnomAD frequency: 0.00001  dbSNP: rs756382502
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810493 SCV000950696 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2022-09-26 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 87 of the SDHC protein (p.Met87Leu). This variant is present in population databases (rs756382502, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 654515). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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.
Ambry Genetics RCV002424899 SCV002743008 likely benign Hereditary cancer-predisposing syndrome 2019-09-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
All of Us Research Program, National Institutes of Health RCV004001724 SCV004839535 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-12-01 criteria provided, single submitter clinical testing

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