Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076478 | SCV000107507 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| Gene |
RCV000479442 | SCV000567757 | pathogenic | not provided | 2015-08-28 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted MSH2 c.2458+1G>A or IVS14+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 14 of the MSH2 gene. The variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least one individual with a suggestive history of Lynch syndrome (Mangold 2005). we consider this variant to be pathogenic. |
| Ambry Genetics | RCV000491889 | SCV000580590 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-01-25 | criteria provided, single submitter | clinical testing | Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000479442 | SCV000601466 | likely pathogenic | not provided | 2017-04-13 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000704889 | SCV000833861 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2019-02-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 14 of the MSH2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with suspected Lynch syndrome (PMID: 15849733). ClinVar contains an entry for this variant (Variation ID: 90976). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Color | RCV000491889 | SCV000908329 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-21 | criteria provided, single submitter | clinical testing |