ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.588+11G>C (rs4647258)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000490567 SCV000106777 benign Lynch syndrome I 2014-10-10 reviewed by expert panel research MAF >1%
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078419 SCV000110267 benign not specified 2013-06-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000030228 SCV000443328 likely benign Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580337 SCV000684845 benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078419 SCV000805975 benign not specified 2016-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000059818 SCV001756426 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030228 SCV000052895 benign Lynch syndrome 2010-09-28 no assertion criteria provided clinical testing
Narod's Lab, University of Toronto RCV000059818 SCV000091388 not provided not provided no assertion provided not provided
Mayo Clinic Laboratories, Mayo Clinic RCV000078419 SCV000257106 benign not specified no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355103 SCV001549886 benign Malignant tumor of breast no assertion criteria provided clinical testing The MLH1 c.588+11G>C variant was not identified in the literature nor was it identified in the MutDB, UMD-LSDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database. The variant was identified in dbSNP (ID: rs4647258) “With other allele”, ClinVar (classified benign, reviewed by an expert panel (2014); submitters: benign by InSIGHT, EGL Genetic Diagnostics (Eurofins Clinical Diagnostics), Mayo Clinic, Laboratory Corporation of America, likely benign by Illumina, and classification not provided by Narod Lab (University of Toronto)), Clinvitae (4x), Insight Colon Cancer Gene Variant Database (1x class 1), Insight Hereditary Tumors Database, and in control databases in 812 of 277078 chromosomes at a frequency of 0.002931 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 754 (7 homozygous) of 24020 chromosomes (freq: 0.03), Other in 4 of 6460 chromosomes (freq: 0.0006), Latino in 47 of 34416 chromosomes (freq: 0.001), European Non-Finnish in 6 of 126604 chromosomes (freq: 0.00005), and South Asian in 1 of 30782 chromosomes (freq: 0.00003) while not observed in the Ashkenazi Jewish, East Asian and European Finnish populations. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000078419 SCV001808972 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000078419 SCV001905972 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000078419 SCV001926099 benign not specified 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.