ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.4002-22_4002-10delinsAAGGG (rs878853744)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229717 SCV000283837 uncertain significance Lynch syndrome 2015-11-02 criteria provided, single submitter clinical testing This sequence change falls in intron 9 of the MSH6 mRNA. It does not directly change the encoded amino acid sequence of the MSH6 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000481439 SCV000571530 uncertain significance not provided 2017-08-22 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.4002-22_4002-10del13insAAGGG or IVS9-22_IVS9-10del13insAAGGG and consists of a deletion of 13 nucleotides and insertion of 5 nucleotides in intron 9 of the MSH6 gene. The normal sequence, with the bases that are deleted and inserted in brackets, is cttttt[del13][insaaggg]aatt. Multiple in silico models predict this variant to destroy the nearby natural splice acceptor site and to possibly cause abnormal gene splicing; however, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 c.4002-22_4002-10del13insAAGGG was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). The nucleotides that are deleted are not conserved. Based on currently available information, it is unclear whether this variant is pathogenic or benign. We consider it to be a variant of uncertain significance.

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