ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.403G>A (p.Val135Met) (rs201585157)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163306 SCV000213834 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-18 criteria provided, single submitter clinical testing The p.V135M variant (also known as c.403G>A), located in coding exon 4 of the SDHB gene, results from a G to A substitution at nucleotide position 403. The valine at codon 135 is replaced by methionine, an amino acid with highly similar properties. This alteration was identified in 1 of 572 individuals who underwent exome sequencing due to a phenotype unrelated to a history of cancer (atherosclerosis) (Johnston JJ et al. Am. J. Hum. Genet. 2012 Jul;91:97-108). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000230410 SCV000287773 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-11-02 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 135 of the SDHB protein (p.Val135Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs201585157, ExAC 0.009%). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 41770). 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: Probably Damaging; Align-GVGD: Class C0). 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.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034687 SCV000043486 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.