ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.521T>C (p.Ile174Thr) (rs200301019)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467690 SCV000554014 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2016-08-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 174 of the SDHB protein (p.Ile174Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SDHB-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001023754 SCV001185672 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-03 criteria provided, single submitter clinical testing The p.I174T variant (also known as c.521T>C), located in coding exon 5 of the SDHB gene, results from a T to C substitution at nucleotide position 521. The isoleucine at codon 174 is replaced by threonine, an amino acid with similar properties. This amino acid position is not 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.

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