ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.884+3A>G (rs267607803)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221867 SCV000273706 pathogenic Hereditary cancer-predisposing syndrome 2019-02-03 criteria provided, single submitter clinical testing RNA Studies;Good segregation with disease (lod 1.5-3 = 5-9 meioses);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Well-characterized mutation at same position;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000629748 SCV000750704 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-11-29 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the MLH1 gene. It does not directly change the encoded amino acid sequence of the MLH1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colorectal cancer (PMID: 11208710). ClinVar contains an entry for this variant (Variation ID: 90413). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000663124 SCV000786258 likely pathogenic Lynch syndrome II 2018-03-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985790 SCV001134325 uncertain significance not provided 2018-12-12 criteria provided, single submitter clinical testing

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