ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.307A>G (p.Met103Val) (rs140178341)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227754 SCV000287769 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-10-25 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 103 of the SDHB protein (p.Met103Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs140178341, ExAC 0.1%). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 239429). 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: Possibly Damaging; Align-GVGD: Class C1). 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 RCV000568674 SCV000664492 likely benign Hereditary cancer-predisposing syndrome 2019-12-04 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Other data supporting benign classification
Mendelics RCV000708787 SCV000837736 uncertain significance Cowden syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763773 SCV000894675 uncertain significance Carney-Stratakis syndrome; Paragangliomas 4; Pheochromocytoma 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000986265 SCV001135204 uncertain significance Gastrointestinal stromal tumor 2019-05-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV001294087 SCV001482893 uncertain significance Pheochromocytoma 2019-09-10 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001575148 SCV001802075 uncertain significance not provided 2020-12-17 no assertion criteria provided clinical testing Protein-based in silico analysis supports a deleterious effect. In addition, splice predictors suggest this variant may impact gene splicing. In the absence of RNA or functional studies, the actual effect of this sequence change is unknown.; Observed in an individual with breast cancer (Yehia 2018); This variant is associated with the following publications: (PMID: 32948195, 29684080)

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