ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1039-6dup (rs1553650466)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128968 SCV000172851 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000233923 SCV000283996 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV001719899 SCV000729361 benign not provided 2018-06-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000128968 SCV001345272 likely benign Hereditary cancer-predisposing syndrome 2019-05-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355193 SCV001550007 benign Carcinoma of colon no assertion criteria provided clinical testing The MLH1 c.1039-6dupA variant was identified in dbSNP (ID: rs535965616) as “Benign ,Likely benign, Uncertain significance allele”, Clinvitae database (as Benign), ClinVar database (as Benign, by GeneDx, Ambry and Invitae), the 1000 Genomes Project in 239 of 5008 chromosomes (frequency: 0.047), the Exome Aggregation Consortium database (August 8, 2016) in 1441 (49 homozygous) of 43560 chromosomes (frequency: 0.033) in the following populations: African in 282 of 3072 chromosomes (frequency: 0.091), European in 838 of 21102 chromosomes (frequency: 0.039), Finnish in 75 of 2195 chromosomes (frequency: 0.034), East Asian in 80 of 2738 chromosomes (frequency: 0.029), other in 10 of 354 chromosomes (frequency: 0.028), Latino in 60 of 3678 chromosomes (frequency: 0.01.6 x 10-2) and South Asian in 96 of 10422 chromosomes (frequency: 0.0009). This variant was not identified in the literature nor was it identified in COSMIC, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, InSiGHT Colon Cancer Gene Variant Database (LOVD), Zhejiang Colon Cancer Database (LOVD), GeneInsight - COGR database, UMD and the NHLBI GO Exome Sequencing Project databases. The c.1039-6dupA variant is located in the 3' splice region but does not affect the invariant -1 and -2 positions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing; in addition 2 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.

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.