Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480936 | SCV000567411 | uncertain significance | not provided | 2015-07-23 | criteria provided, single submitter | clinical testing | This variant is denoted MSH6 c.3977T>C at the cDNA level, p.Met1326Thr (M1326T) at the protein level, and results in the change of a Methionine to a Threonine (ATG>ACG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Met1326Thr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Methionine and Threonine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Met1326Thr occurs at a position that is not conserved and is located in the MutS domain V (Terui 2013). A published in silico algorithm predicted this variant to be of uncertain significance, and in house in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function (Terui 2013). Based on currently available information, it is unclear whether MSH6 Met1326Thr is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000574295 | SCV000669986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-30 | criteria provided, single submitter | clinical testing | The p.M1326T variant (also known as c.3977T>C), located in coding exon 9 of the MSH6 gene, results from a T to C substitution at nucleotide position 3977. The methionine at codon 1326 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001348367 | SCV001542667 | benign | Hereditary nonpolyposis colorectal neoplasms | 2023-08-24 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002305 | SCV004821998 | uncertain significance | Lynch syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing |