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	Hereditary nonpolyposis colorectal neoplasms	2019-12-31	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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