Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000536108 | SCV000625089 | pathogenic | Hereditary nonpolyposis colon cancer | 2017-12-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 14 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported in the literature in an individual affected with Lynch syndrome (PMID: 26248088). A different variant affecting this nucleotide (c.1667+1G>T) has been determined to be pathogenic in a family affected with Lynch syndrome (PMID: 21642682). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000563359 | SCV000669523 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-06-19 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Well-characterized mutation at same position |
| 3DMed Clinical Laboratory Inc | RCV000677882 | SCV000804043 | pathogenic | Colon cancer | 2017-11-02 | no assertion criteria provided | clinical testing |