ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.677+1G>A (rs267607778)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075802 SCV000106817 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV000533036 SCV000625183 pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-06-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic. This particular variant has been reported in the literature in a family affected with Lynch syndrome (PMID: 12070261). A different variant affecting this nucleotide (c.677+1G>T) has been determined to be pathogenic (PMID: 27601186, 12624141, 15342696, 17312306). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000663323 SCV000786595 likely pathogenic Lynch syndrome II 2018-06-04 criteria provided, single submitter clinical testing
Color RCV001183308 SCV001349012 likely pathogenic Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing

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