ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.73G>A (p.Ala25Thr) (rs768101924)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000797417 SCV000936972 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-03-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 25 of the SDHB protein (p.Ala25Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs768101924, ExAC 0.02%). This variant has not been reported in the literature in individuals with SDHB-related disease. 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 threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV001026392 SCV001188762 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing The p.A25T variant (also known as c.73G>A) is located in coding exon 2 of the SDHB gene. The alanine at codon 25 is replaced by threonine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 2. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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