Submissions for variant NM_000179.2(MSH6):c.4081T>C (p.Ter1361Gln) (rs765098678)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486271	SCV000565243	uncertain significance	not provided	2015-08-25	criteria provided, single submitter	clinical testing	This variant is denoted MSH6 c.4081T>C at the cDNA level and p.Ter1361GlnextX29 (X1361QextX29) at the protein level. This substitution is located in the stop codon of the MSH6 gene and results in the natural stop codon being changed to a Glutamine (TAG>CAG), resulting in the extension of the protein by 29 amino acids. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. Of note, this variant is in the C-terminal region of MSH6 which is a binding site for MSH2 (Kariola 2002). Based on currently available information, it is unclear whether MSH6 Ter1361GlnextX29 is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000562452	SCV000676113	uncertain significance	Hereditary cancer-predisposing syndrome	2018-04-19	criteria provided, single submitter	clinical testing	Insufficient or conflicting evidence;Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae	RCV000694136	SCV000822567	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2019-12-26	criteria provided, single submitter	clinical testing	This sequence change disrupts the translational stop signal of the MSH6 mRNA. It is expected to extend the length of the MSH6 protein by 29 additional amino acid residues. This variant is present in population databases (rs765098678, ExAC 0.006%). This variant has not been reported in the literature in individuals with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 418334). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color	RCV000562452	SCV000908446	uncertain significance	Hereditary cancer-predisposing syndrome	2019-04-08	criteria provided, single submitter	clinical testing

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