Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000552123 | SCV000624800 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000568062 | SCV000669913 | likely benign | Hereditary cancer-predisposing syndrome | 2017-02-27 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Color Diagnostics, |
RCV000568062 | SCV000690298 | likely benign | Hereditary cancer-predisposing syndrome | 2017-11-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004003684 | SCV004838934 | likely benign | Lynch syndrome | 2023-06-26 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001354586 | SCV001549234 | uncertain significance | Carcinoma of colon | no assertion criteria provided | clinical testing | The MSH6 p.Gly963= variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, MutDB, UMD-LSDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, Insight Hereditary Tumors Database, databases. The variant was identified in dbSNP (ID: rs771726914) as NA, database. The variant was identified in control databases in 5 of 244362 chromosomes at a frequency of 0.00002 increasing the likelihood that this may be a low frequency variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The p.Gly963= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. However, 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as uncertain significance. |