ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.344G>A (p.Arg115Gln) (rs200973284)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766362 SCV000279895 uncertain significance not provided 2020-11-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24728327)
Ambry Genetics RCV000574274 SCV000675069 uncertain significance Hereditary cancer-predisposing syndrome 2016-07-07 criteria provided, single submitter clinical testing The p.R115Q variant (also known as c.344G>A), located in coding exon 4 of the SDHB gene, results from a G to A substitution at nucleotide position 344. The arginine at codon 115 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,503 samples (13,006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 20000 alleles tested) in our clinical cohort. This amino acid position is well conserved through mammals. 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.
Illumina Clinical Services Laboratory,Illumina RCV001101288 SCV001257888 uncertain significance Carney-Stratakis syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001101289 SCV001257889 uncertain significance Hereditary Paraganglioma-Pheochromocytoma Syndromes 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001349603 SCV001543955 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-03-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 115 of the SDHB protein (p.Arg115Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs200973284, ExAC 0.006%). This variant has not been reported in the literature in individuals with SDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 135193). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
ITMI RCV000122001 SCV000086212 not provided not specified 2013-09-19 no assertion provided reference population

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