ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.663A>C (p.Glu221Asp) (rs41557217)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000121575 SCV000149349 likely benign not specified 2018-02-12 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001083709 SCV000166237 benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000115440 SCV000185332 benign Hereditary cancer-predisposing syndrome 2014-07-01 criteria provided, single submitter clinical testing Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene;Internal frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000121575 SCV000592573 likely benign not specified 2016-07-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000121575 SCV000604274 likely benign not specified 2016-12-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588752 SCV000695925 benign not provided 2016-10-28 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.663A>C (p.Glu221Asp) variant causes a missense change involving a non-conserved nucleotide with 5/5 in silico tools predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 75/119664 (1/1595), which is approximately 4 times the estimated maximal expected allele frequency for a pathogenic MSH6 variant of 1/7037 (0.0001421), suggesting this variant is likely a benign polymorphism. The variant of interest has been reported in multiple affected individuals via publications. In addition, multiple clinical diagnostic laboratories/databases cite the variant as "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659887 SCV000781782 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2016-11-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000588752 SCV000805910 likely benign not provided 2017-10-12 criteria provided, single submitter clinical testing
GeneKor MSA RCV000115440 SCV000821800 likely benign Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000075021 SCV000837870 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588752 SCV000889505 benign not provided 2018-08-15 criteria provided, single submitter clinical testing
Color RCV000115440 SCV000902593 benign Hereditary cancer-predisposing syndrome 2016-04-11 criteria provided, single submitter clinical testing
Mendelics RCV000659887 SCV001135794 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000588752 SCV001152287 uncertain significance not provided 2018-06-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000659887 SCV001302617 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2019-05-01 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ITMI RCV000121575 SCV000085771 not provided not specified 2013-09-19 no assertion provided reference population
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000121575 SCV000691920 uncertain significance not specified no assertion criteria provided clinical testing
True Health Diagnostics RCV000115440 SCV000788058 likely benign Hereditary cancer-predisposing syndrome 2017-08-30 no assertion criteria provided clinical testing

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.