ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1558+14G>A (rs41562513)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030214 SCV000106241 no known pathogenicity Lynch syndrome 2013-09-05 reviewed by expert panel research MAF >1%
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030214 SCV000052881 benign Lynch syndrome 2011-08-18 criteria provided, single submitter clinical testing Converted during submission to Benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078416 SCV000110262 benign not specified 2013-01-14 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078416 SCV000303145 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000616483 SCV000443337 benign Lynch syndrome II 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Health, Inc RCV000449421 SCV000537353 benign Hereditary cancer-predisposing syndrome 2014-11-26 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000616483 SCV000781758 uncertain significance Lynch syndrome II 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000078416 SCV001156601 benign not specified 2018-07-06 criteria provided, single submitter clinical testing
Invitae RCV001510183 SCV001717148 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV001650849 SCV001868837 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28932927, 27629256, 27884173, 15996210, 24689082, 23588873, 16395668)
Pathway Genomics RCV000144605 SCV000189932 benign Lynch syndrome I 2014-07-24 no assertion criteria provided clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000078416 SCV000257053 benign not specified no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354017 SCV000592408 benign Carcinoma of colon no assertion criteria provided clinical testing The c.1558+14G>A variant has been identified in 10 out of 670 proband chromosomes (frequency 0.015) in individuals with colorectal and breast cancer as well as the transitional cell carcinoma of the urinary tract; however no normal population controls were included in these studies (Furihata 2001, Kurzawski 2002, Murata 2002, Palicio 2002, Ward 2002, Lee 2005). It is listed in dbSNP database presented “With non-pathogenic allele” (ID#: rs41562513) with a “global minor allele frequency of 0.054 (1000 genomes), therefore increasing the likelihood that this variant is benign. One study demonstrated by RT-PCR that this variant did not affect splicing (Auclari_2006_16395668), increasing the likelihood this variant does not have clinical significance. This variant is located in the 5' splice region but does not affect the invariant +1 and +2 positions, or positions +3 to +6 that are part of the splicing consensus sequence which sometimes affect splicing. In addition, in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts no change in the splice site prediction score. In summary, based on the above information, this variant is classified as benign
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000616483 SCV000734267 benign Lynch syndrome II no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000078416 SCV001798604 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000078416 SCV001906015 benign not specified no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV000078416 SCV001919830 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000078416 SCV001956792 benign not specified no assertion criteria provided clinical testing

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