ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1731+8T>C (rs370108219)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410753 SCV000489307 likely benign Lynch syndrome II 2016-09-14 criteria provided, single submitter clinical testing
GeneDx RCV000419663 SCV000513629 benign not specified 2015-06-17 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.
Invitae RCV000475237 SCV000555979 likely benign not provided 2019-02-01 criteria provided, single submitter clinical testing
Color RCV000584327 SCV000689834 likely benign Hereditary cancer-predisposing syndrome 2017-10-06 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000419663 SCV000919652 uncertain significance not specified 2018-01-02 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.1731+8T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 3/245974 control chromosomes at a frequency of 0.0000122, which does not exceed the estimated maximal expected allele frequency of a pathogenic MLH1 variant (0.0007105). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a VUS-possibly benign, until additional information becomes available.

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