ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.69A>G (p.Glu23=) (rs63750555)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000161941 SCV000211926 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162712 SCV000213173 likely benign Hereditary cancer-predisposing syndrome 2015-01-16 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506165 SCV000601409 uncertain significance not specified 2017-06-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162712 SCV000684861 likely benign Hereditary cancer-predisposing syndrome 2015-05-05 criteria provided, single submitter clinical testing
Counsyl RCV000663024 SCV000786048 likely benign Lynch syndrome II 2018-02-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000506165 SCV000917645 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
GeneDx RCV001534755 SCV001751702 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354478 SCV001549105 likely benign Lynch syndrome no assertion criteria provided clinical testing The MLH1 p.Glu23= variant was not identified in the literature nor was it identified in the UMD-LSDB. The variant was identified in dbSNP (ID: rs63750555) as "With Uncertain significance allele" and in ClinVar (classified as likely benign by Invitae, Ambry Genetics, Color and Counsyl; as uncertain significance by one submitter). The variant was identified in control databases in 2 of 246094 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in European population in 2 of 111564 chromosomes (freq: 0.00002), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Glu23= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer,) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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