Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000533753 | SCV000625411 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2019-08-14 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with glutamic acid at codon 923 of the MSH2 protein (p.Val923Glu). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is present in population databases (rs146421227, ExAC 0.002%). This variant has been reported in the literature in individuals from several families affected with Lynch syndrome (PMID: 12112654, 21431882, 18566915, 17101317). ClinVar contains an entry for this variant (Variation ID: 91043). Experimental studies report contradictory results. This missense change was shown to cause a mild reduction in mismatch binding and release capacity of MSH2 (PMID: 18951462), but behaved as wild-type by mismatch repair activity in vitro (PMID: 17101317, 21431882) 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. |
Ambry Genetics | RCV001016538 | SCV001177501 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-20 | criteria provided, single submitter | clinical testing | Insufficient evidence |
Color | RCV001016538 | SCV001353063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-25 | criteria provided, single submitter | clinical testing | |
CSER _CC_NCGL, |
RCV000148640 | SCV000190355 | uncertain significance | Colorectal cancer, non-polyposis | 2014-06-01 | no assertion criteria provided | research |