ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1896+5G>A (rs759870594)

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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 RCV000575544 SCV000669548 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000764496 SCV000895567 uncertain significance Turcot syndrome; Muir-Torré syndrome; Lynch syndrome II 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000575544 SCV000908648 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-26 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000998018 SCV001153850 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV001041310 SCV001204916 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-04-11 criteria provided, single submitter clinical testing This sequence change falls in intron 16 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 present in population databases (rs759870594, ExAC 0.02%). This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 483545). 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.

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