ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.468_471del (p.Glu158fs) (rs587779941)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115431 SCV000149340 pathogenic not provided 2018-07-09 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in MSH6 is denoted c.468_471delAAAG at the cDNA level and p.Glu158ProfsX15 (E158PfsX15) at the protein level. The normal sequence, with the bases that are deleted in braces, is AATC{AAAG}GAAG. The deletion causes a frameshift which changes a Glutamic Acid to a Proline at codon 158, and creates a premature stop codon at position 15 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. MSH6 c.468_471delAAAG has been observed in an individual with Lynch syndrome (Goldberg 2014). We consider this variant to be pathogenic.
Invitae RCV000477380 SCV000551073 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-05-15 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotide from exon 3 of the MSH6 mRNA (c.468_471delAAAG), causing a frameshift at codon 158. This creates a premature translational stop signal (p.Glu158Profs*15) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic. This particular variant has been reported in an individual affected with Lynch syndrome (PMID: 25430799). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000491425 SCV000580151 pathogenic Hereditary cancer-predisposing syndrome 2017-12-07 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000491425 SCV000905446 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing

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