ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3788G>A (p.Arg1263His) (rs147852216)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656903 SCV000149332 uncertain significance not provided 2019-01-16 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3788G>A at the cDNA level, p.Arg1263His (R1263H) at the protein level, and results in the change of an Arginine to a Histidine (CGC>CAC). This variant has been reported in an individual with Ewing sarcoma, and individual with breast cancer, and in 1/50 healthy Central Asian individuals undergoing whole genome sequencing (Bodian 2014, Tung 2015, Ballinger 2016). Of note, the participants in the Bodian et al. (2014) study were younger than 50 years old thus the unaffected status of this individual may not be significant. MSH6 Arg1263His was observed at an allele frequency of 0.08% (25/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located within the ATPase domain (Warren 2007, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH6 Arg1263His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV001079217 SCV000254321 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000115423 SCV000292204 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115423 SCV000580213 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-27 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Counsyl RCV000662548 SCV000785130 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2017-05-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656903 SCV000889494 uncertain significance not provided 2018-03-21 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764435 SCV000895492 uncertain significance Endometrial carcinoma; Turcot syndrome; Hereditary nonpolyposis colorectal cancer type 5 2018-10-31 criteria provided, single submitter clinical testing
ITMI RCV000121588 SCV000085784 not provided not specified 2013-09-19 no assertion provided reference population

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