ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1050A>G (p.Pro350=) (rs137937003)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000588641 SCV000166239 benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163310 SCV000213838 likely benign Hereditary cancer-predisposing syndrome 2014-10-08 criteria provided, single submitter clinical testing
GeneDx RCV000443419 SCV000513620 benign not specified 2015-03-24 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.
Color RCV000163310 SCV000537502 likely benign Hereditary cancer-predisposing syndrome 2015-11-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588641 SCV000696094 likely benign not provided 2016-12-22 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.1050A>G (p.Pro350Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome while 5/5 splice prediction tools predict no significant impact on normal splicing for this substitution. This variant was found in 15/111028 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.0008542 (9/10536). This frequency is slightly higher than the estimated maximal expected allele frequency of a pathogenic MLH1 variant (0.0007105), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant was reported in a MSI-High Spanish colorectal cancer patient who fulfilled the Bethesda criteria for HNPCC. The patient also harbored MSH6 c.1677 C>T (p.Cys559Cys) variant and the tumor IHC was positive for MLH1, MSH2, and MSH6 . He presented with multiple tumors with one of the showing LOH of the variant allele further indicating a neutral impact. Additionally, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
PreventionGenetics,PreventionGenetics RCV000588641 SCV000805941 likely benign not provided 2016-12-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588641 SCV000888170 benign not provided 2018-01-09 criteria provided, single submitter clinical testing
Mendelics RCV000987168 SCV001136400 likely benign Lynch syndrome II 2019-05-28 criteria provided, single submitter clinical testing

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