ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.112C>T (p.Arg38Cys) (rs202119350)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409187 SCV000487960 uncertain significance Paragangliomas 4 2015-12-08 criteria provided, single submitter clinical testing
Invitae RCV000456572 SCV000554010 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 38 of the SDHB protein (p.Arg38Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs202119350, ExAC 0.009%). This variant has been reported in individuals affected with paraganglioma (PMID: 23660872, Invitae). ClinVar contains an entry for this variant (Variation ID: 371801). 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 disruptive, 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 RCV000570971 SCV000675068 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-22 criteria provided, single submitter clinical testing The p.R38C variant (also known as c.112C>T), located in coding exon 2 of the SDHB gene, results from a C to T substitution at nucleotide position 112. The arginine at codon 38 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been previously identified in an individual with metastatic parganglioma (de Cubas AA et al. Endocr. Relat. Cancer. 2013 Aug;20(4):477-93). 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.
Mendelics RCV000708789 SCV000837738 uncertain significance Cowden syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763775 SCV000894677 uncertain significance Carney-Stratakis syndrome; Paragangliomas 4; Pheochromocytoma 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000986267 SCV001135206 uncertain significance Gastrointestinal stromal tumor 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000986267 SCV002030195 uncertain significance Gastrointestinal stromal tumor 2021-04-02 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Gharavi Laboratory,Columbia University RCV000782212 SCV000920698 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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