ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.655A>G (p.Met219Val)

dbSNP: rs2077968991
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001880338 SCV002118580 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2021-05-25 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 219 of the SDHB protein (p.Met219Val). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and valine. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHB protein function. 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.
Ambry Genetics RCV004946773 SCV005500631 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-24 criteria provided, single submitter clinical testing The p.M219V variant (also known as c.655A>G), located in coding exon 7 of the SDHB gene, results from an A to G substitution at nucleotide position 655. The methionine at codon 219 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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