Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000165796 | SCV000216543 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-02-23 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient evidence,Conflicting evidence |
Soonchunhyang University Bucheon Hospital, |
RCV000410248 | SCV000267401 | uncertain significance | Lynch syndrome I | 2016-03-18 | criteria provided, single submitter | reference population | |
Counsyl | RCV000410248 | SCV000488061 | uncertain significance | Lynch syndrome I | 2015-12-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000524376 | SCV000548225 | uncertain significance | Hereditary nonpolyposis colon cancer | 2018-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 688 of the MSH2 protein (p.Met688Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is present in population databases (rs63750790, ExAC 0.06%). This variant has been reported in individuals affected with colorectal and endometrial cancer, as well as in individuals with hereditary nonpolyposis colorectal cancer (PMID: 9559627, 10777691, 14499697, 23741719). It has also been observed in three control individuals in a healthy cohort of 179 individuals (PMID: 15527911). ClinVar contains an entry for this variant (Variation ID: 90875). Functional studies do not agree on the effect of this variant on mismatch repair activity (PMID: 17720936, 22739024, 21309037). A different missense substitution at this codon (p.Met688Arg) has been determined to be pathogenic (PMID: 22739024, 10080150, 15075785, 20010080, 22739024, 21239990, 21225464). This suggests that the methionine residue is critical for MSH2 protein function and that other missense substitutions at this position may also be pathogenic. 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 | RCV000165796 | SCV000685006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-26 | criteria provided, single submitter | clinical testing |