Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165173 | SCV000215885 | likely benign | Hereditary cancer-predisposing syndrome | 2014-10-13 | 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. |
| Gene |
RCV000756724 | SCV000568854 | uncertain significance | not provided | 2016-05-16 | criteria provided, single submitter | clinical testing | This variant is denoted STK11 c.1167C>G at the DNA level. Although this variant is silent at the coding level, preserving an Alanine at codon 389, it is predicted to cause the gain of a cryptic splice donor site 150bp upstream of the natural splice donor site for intron 9. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. STK11 c.1167C>G was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The nucleotide which is altered, a cytosine (C) at base 1167, is not conserved. Based on currently available evidence, it is unclear whether STK11 c.1167C>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Invitae | RCV000558075 | SCV000629070 | likely benign | Peutz-Jeghers syndrome | 2023-10-28 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000756724 | SCV000884616 | uncertain significance | not provided | 2018-06-19 | criteria provided, single submitter | clinical testing | The STK11 c.1167C>G; p.Ala389Ala variant (rs547919101), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 185703). This variant is found in the general population with an overall allele frequency of 0.004% (9/237420 alleles) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide, but computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating or strengthening a novel cryptic donor splice site upstream of the canonical donor site. However, given the lack of clinical and functional data, the significance of the p.Ala389Ala variant is uncertain at this time. |
| Color Diagnostics, |
RCV000165173 | SCV000903948 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-04 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000558075 | SCV002057316 | likely benign | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000165173 | SCV002531649 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-27 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV000558075 | SCV004819000 | likely benign | Peutz-Jeghers syndrome | 2023-05-08 | criteria provided, single submitter | clinical testing |