ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.200T>C (p.Met67Thr)

dbSNP: rs1287584713
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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 RCV000699006 SCV000827698 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2022-03-27 criteria provided, single submitter clinical testing 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 576498). This missense change has been observed in individual(s) with clinical features of SDHC-related conditions (PMID: 30050099). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 67 of the SDHC protein (p.Met67Thr).
Ambry Genetics RCV002422550 SCV002722876 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-12 criteria provided, single submitter clinical testing The p.M67T variant (also known as c.200T>C), located in coding exon 4 of the SDHC gene, results from a T to C substitution at nucleotide position 200. The methionine at codon 67 is replaced by threonine, an amino acid with similar properties. This alteration, identified as a variant of unknown significance, was identified in an individual with a paraganglioma (Richter S et al. Genet. Med., 2019 03;21:705-717). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV003999687 SCV004826115 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 67 of the SDHC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hereditary paranganglioma-pheochromocytoma syndrome (PMID: 30050099). This variant has been identified in 1/248998 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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