ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.365A>G (p.Asn122Ser) (rs1557741472)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020819 SCV001182349 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-18 criteria provided, single submitter clinical testing The p.N122S variant (also known as c.365A>G), located in coding exon 4 of the SDHB gene, results from an A to G substitution at nucleotide position 365. The asparagine at codon 122 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved however, serine is a reference amino acid in several 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.
Invitae RCV001067820 SCV001232901 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-11-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 122 of the SDHB protein (p.Asn122Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related conditions. 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 serine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional 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.

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