ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3897_3931dup (p.Glu1311fs) (rs1064793895)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491494 SCV000580094 pathogenic Hereditary cancer-predisposing syndrome 2014-09-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000491494 SCV000690420 pathogenic Hereditary cancer-predisposing syndrome 2017-02-21 criteria provided, single submitter clinical testing
GeneDx RCV000478927 SCV000567296 pathogenic not provided 2015-07-15 criteria provided, single submitter clinical testing This duplication of 35 nucleotides in MSH6 is denoted c.3897_3931dup35 at the cDNA level and p.Glu1311AlafsX28 (E1311AfsX28) at the protein level. The surrounding sequence is AGAGG[dup35]AAGT. The duplication causes a frameshift, which changes a Glutamic Acid to an Alanine at codon 1311, and creates a premature stop codon at position 28 of the new reading frame. Even though this frameshift occurs in the 3' end of the gene, it is significant since the last 50 correct amino acids are replaced by 27 incorrect ones. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation and is located upstream of other frameshift variants; one specifically, MSH6 c.3984_3987dupGTCA, has been observed internally and published in several families with Lynch syndrome (Peterlongo 2003, Goldberg 2010, Raskin 2011). we consider this variant to be pathogenic.

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