ClinVar Miner

Submissions for variant NM_001281492.1(MSH6):c.3626_3627dup (p.Ser1210fs) (rs876661127)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000223267 SCV000279623 uncertain significance not specified 2015-11-18 criteria provided, single submitter clinical testing This duplication of 2 nucleotides in MSH6 is denoted c.4016_4017dupCT at the cDNA level and p.Ser1340LeufsX7(S1340LfsX7) at the protein level. The normal sequence, with the bases that are duplicated in braces, is CTGG[CT]AGTG. The duplication causes a frameshift, which changes a Serine to a Leucine at codon 1340, and creates a premature stop codon at position 7 of the new reading frame. As this duplication is in the last exon of the gene, nonsense mediated decay is not expected to occur. 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. Based on currently available information, it is unclear whether this duplication is a pathogenic variant or a benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000470892 SCV000551204 uncertain significance Hereditary nonpolyposis colon cancer 2019-01-05 criteria provided, single submitter clinical testing This sequence change inserts 2 nucleotide in exon 10 of the MSH6 mRNA (c.4016_4017dupCT), causing a frameshift at codon 1340. This creates a premature translational stop signal in the last exon of the MSH6 mRNA (p.Ser1340Leufs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 21 amino acids of the MSH6 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MSH6-related disease. ClinVar contains an entry for this variant (Variation ID: 234626). Experimental studies have not been reported for this truncating variant and it is currently unknown if the last 21 amino acids of the MSH6 protein are critical for its function. In summary, this variant is a rare truncation with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000487491 SCV000574718 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-10 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000487491 SCV000909496 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-23 criteria provided, single submitter clinical testing

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