ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.303T>G (p.Gly101=) (rs4647220)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075626 SCV000106628 likely benign Lynch syndrome 2013-09-05 reviewed by expert panel research Synonymous substitution with no effect on splicing & MAF 0.01-1%
Invitae RCV001084168 SCV000166253 benign Hereditary nonpolyposis colon cancer 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000121356 SCV000211152 benign not specified 2014-08-15 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.
Ambry Genetics RCV000160567 SCV000212812 benign Hereditary cancer-predisposing syndrome 2019-10-23 criteria provided, single submitter clinical testing RNA Studies;In silico models in agreement (benign);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV001094909 SCV000443325 likely benign Lynch syndrome II 2019-02-22 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000121356 SCV000592347 benign not specified 2016-11-09 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000121356 SCV000595799 likely benign not specified 2016-06-15 criteria provided, single submitter clinical testing
Color RCV000160567 SCV000684815 benign Hereditary cancer-predisposing syndrome 2015-04-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587630 SCV000696159 benign not provided 2016-05-20 criteria provided, single submitter clinical testing Variant summary: The c.303T>G (p.Gly101=) in MLH1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing which was supported by a RNA-based functional assay by Thompson et al (2012). The variant is present in the control population dataset of ExAC at frequency of 0.0027 (331/121138) predominantly in individuals of South Asian descent (0.02; 329/16482 chrs) including 5 homozygous occurrences, suggesting that it is a polymorphism mainly found in South Asian population. The variant of interest been reported in affected individuals in whom either another known pathogenic variant was identified (Internal LCA data) or ICH results pointed out mutation(s) in other MMR genes (Mangold, 2007). In addition, the variant is cited as Benign/Likely Benign by reputable databases/clinical laboratories. Taking together, the variant is classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587630 SCV000888182 benign not provided 2017-08-31 criteria provided, single submitter clinical testing
ITMI RCV000121356 SCV000085535 not provided not specified 2013-09-19 no assertion provided reference population

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