Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000232871 | SCV000283861 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000571890 | SCV000662355 | likely benign | Hereditary cancer-predisposing syndrome | 2015-03-20 | 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, |
RCV000571890 | SCV000690492 | likely benign | Hereditary cancer-predisposing syndrome | 2017-07-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000610225 | SCV000729024 | benign | not specified | 2015-05-26 | 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. |
Department of Pathology and Laboratory Medicine, |
RCV001354904 | SCV001549628 | likely benign | Lynch syndrome | no assertion criteria provided | clinical testing | The MSH6 p.Thr319= variant was not identified in the literature nor was it identified in the COGR, Cosmic, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs375210430) as "With Likely benign allele", and in ClinVar (classified as likely benign by Invitae, Ambry Genetcs, Color Genomics, GeneDx). The variant was identified in control databases in 4 of 246054 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 1 of 33574 chromosomes (freq: 0.00003), European in 3 of 111556 chromosomes (freq: 0.00003), it was not observed in the African, Other, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Thr319= 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) 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. |