ClinVar Miner

Submissions for variant NM_003000.3(SDHB):c.158G>A (p.Gly53Glu) (rs34916635)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163315 SCV000213843 benign Hereditary cancer-predisposing syndrome 2015-09-06 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Intact protein function observed in appropriate functional assay(s)
Invitae RCV001081765 SCV000261941 benign Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2020-12-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000266464 SCV000351429 likely benign Carney-Stratakis syndrome 2019-04-21 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000323978 SCV000351430 likely benign Hereditary Paraganglioma-Pheochromocytoma Syndromes 2019-04-21 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx RCV000713176 SCV000730537 likely benign not provided 2020-08-25 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23512077, 25694510, 21979946, 25394176, 19802898, 18458953, 23072324, 20923864, 28873162, 30152102)
Athena Diagnostics Inc RCV000713176 SCV000843759 benign not provided 2018-01-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000602372 SCV001478595 benign not specified 2021-01-17 criteria provided, single submitter clinical testing Variant summary: SDHB c.158G>A (p.Gly53Glu) results in a non-conservative amino acid change located in the 2Fe-2S ferredoxin-type iron-sulfur binding domain (IPR010141) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00053 in 251378 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is higher than the estimated maximal expected allele frequency for a pathogenic variant in SDHB causing Hereditary Paraganglioma-Pheochromocytoma Syndrome phenotype (2.2e-07), strongly suggesting that the variant is benign. Although, this variant has been reported in the literature (example, Fishbein_2013, Cox_2018), to our knowledge, no occurrence of c.158G>A in individuals affected with Hereditary Paraganglioma-Pheochromocytoma Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=3)/likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign.
GenomeConnect, ClinGen RCV000709876 SCV000840213 not provided Gastrointestinal stromal tumor; Carney-Stratakis syndrome; Paragangliomas 4; Pheochromocytoma; Cowden syndrome 1 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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