Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573811 | SCV000662464 | likely benign | Hereditary cancer-predisposing syndrome | 2016-04-07 | 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, |
RCV000573811 | SCV000690186 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-21 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000609058 | SCV000729030 | likely benign | not specified | 2018-02-22 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000875742 | SCV001018211 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-31 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004000873 | SCV004835375 | likely benign | Lynch syndrome | 2023-04-10 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001356316 | SCV001551450 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The MSH6 p.Arg411= variant was not identified in the literature nor was it identified in the MutDB, LOVD 3.0, UMD-LSDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs554843104), ClinVar (classified likely benign by Ambry Genetics, Color Genomics Inc and GeneDx), Clinvitae (1x), Cosmic (1x in a malignant melanoma), and in control databases in 5 of 246106 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). It was observed in the South Asian population in 5 of 30782 chromosomes (freq: 0.0002) but not in the African, Other, Latino, European Non-Finnish, Ashkenazi Jewish, East Asian and Finnish populations. The p.Arg411= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |