Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000162762 | SCV000213239 | likely benign | Hereditary cancer-predisposing syndrome | 2019-09-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
| Invitae | RCV003743603 | SCV000647442 | likely benign | Familial adenomatous polyposis 1 | 2023-11-16 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000614189 | SCV000722485 | likely benign | not specified | 2017-08-27 | 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. |
| Color Diagnostics, |
RCV000162762 | SCV001353118 | likely benign | Hereditary cancer-predisposing syndrome | 2019-02-06 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355301 | SCV001550151 | uncertain significance | Endometrial carcinoma | no assertion criteria provided | clinical testing | The APC p.Arg1114= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, MutDB, LOVD 3.0, UMD-LSDB, or Zhejiang University, databases. The variant was identified in dbSNP (ID: rs786201145) as "With Uncertain significance allele", and in ClinVar database (classified as likely benign by Ambry Genetics and GeneDx; as uncertain significance by Invitae). The variant was identified in control databases in 1 of 245228 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 1 of 110948 chromosomes (freq: 0.000009), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Arg1114= 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. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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 a variant of uncertain significance. |