ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.4067_4071inv (p.Leu1356_Ile1357delinsTer)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485533 SCV000565941 uncertain significance not provided 2015-03-10 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.4067_4071delTGATTinsAATCA at the cDNA level and p.Leu1356Ter (L1356X) at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is ACTT[delTGATT][insAATCA]AAGG. This in frame deletion and insertion creates a nonsense variant, which changes a Leucine to a premature stop in the last exon of the protein, exon 10, resulting in the loss of the last five amino acids of the protein are lost, the clinical significance of which is unclear. The lost region is conserved among mammals and is not within a known functional domain (UniProt). This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. While other variants also resulting in truncation of the MSH6 protein have been reported in the lost region, none, to our knowledge, have been proven to have pathogenic effect (Johnston 2012, Martinez 2010, Wasielewski 2010). Based on the currently available information, we consider MSH6 Leu1356Ter to be a variant of uncertain significance.
Ambry Genetics RCV000570455 SCV000670031 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-24 criteria provided, single submitter clinical testing Insufficient evidence

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