ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.42A>C (p.Thr14=) (rs369737664)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000126779 SCV000213203 likely benign Hereditary cancer-predisposing syndrome 2014-07-03 criteria provided, single submitter clinical testing
Color RCV000126779 SCV000684829 likely benign Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
GeneDx RCV000212511 SCV000170302 benign not specified 2014-05-08 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.
Integrated Genetics/Laboratory Corporation of America RCV000585926 SCV000696164 likely benign not provided 2017-06-23 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.42A>C (p.Thr14Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 11/121284 control chromosomes, predominantly observed in the East Asian subpopulation at a frequency of 0.001271 (11/8654). This frequency is about 2 times 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 East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported as a confirmed germline variant in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is currently classified as likely benign.
Invitae RCV000122977 SCV000166255 benign Hereditary nonpolyposis colon cancer 2017-12-18 criteria provided, single submitter clinical testing

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