ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3802-7_3802-4del (rs876661171)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000219815 SCV000279708 uncertain significance not provided 2018-07-10 criteria provided, single submitter clinical testing This variant is denoted MSH6 c.3802-7_3802-4delTCTT or IVS8-7_IVS8-4delTCTT and consists of a deletion of four nucleotides at the -4 through -7 positions in intron 8 of the MSH6 gene. The normal sequence with the bases that are deleted in brackets is tctt[deltctt]aagG, where the capital letters are exonic and lowercase are intronic. Using alternate nomenclature, this variant may be defined as c.3802-13_3802-10delTTTC. In silico analyses, which include splice predictors and evolutionary conservation, are inconsistent in their assessment as to whether or not the variant is damaging. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016).This variant has not, to our knowledge, been published in the literature as either a pathogenic germline variant or a benign polymorphism. Based on the currently available information, we consider MSH6 c.3802-7_3802-4delTCTT to be a variant of uncertain significance.
Ambry Genetics RCV000491776 SCV000580092 likely pathogenic Hereditary cancer-predisposing syndrome 2017-03-16 criteria provided, single submitter clinical testing Insufficient evidence;RNA Studies;Other data supporting pathogenic classification;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Moderate segregation with disease (at least 3 informative meioses) for rare diseases.
Color RCV000491776 SCV000904155 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-05 criteria provided, single submitter clinical testing
Invitae RCV000801331 SCV000941105 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-11-27 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the MSH6 gene. 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). This variant has been observed in several individuals affected with Lynch syndrome-associated cancers (PMID: 21520333, external communication). It has also been observed to segregate with Lynch syndrome-associated cancers in a family (external communication). ClinVar contains an entry for this variant (Variation ID: 234703). Experimental studies have shown that this variant disrupts mRNA splicing (external communication). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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