Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000163139 | SCV000213655 | likely benign | Hereditary cancer-predisposing syndrome | 2015-02-09 | 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. |
Labcorp Genetics |
RCV000198223 | SCV000254536 | benign | Peutz-Jeghers syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000427198 | SCV000519100 | likely benign | not specified | 2017-08-15 | 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800476 | SCV000602204 | likely benign | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000163139 | SCV000691463 | likely benign | Hereditary cancer-predisposing syndrome | 2016-04-27 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000198223 | SCV000784886 | likely benign | Peutz-Jeghers syndrome | 2017-01-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV003492670 | SCV000839424 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000427198 | SCV000920281 | likely benign | not specified | 2024-08-20 | criteria provided, single submitter | clinical testing | Variant summary: STK11 c.1038C>T alters a conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.3e-05 in 1611152 control chromosomes (gnomAD database v4). The observed variant frequency is approximately 7 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Peutz-Jeghers Syndrome phenotype (6.3e-06). c.1038C>T has been reported in the literature in individuals affected with Breast Cancer (Guindalini_2022) without evidence for causality. These report(s) do not provide unequivocal conclusions about association of the variant with Peutz-Jeghers Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 26010451). ClinVar contains an entry for this variant (Variation ID: 184026). Based on the evidence outlined above, the variant was classified as likely benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798570 | SCV002042759 | uncertain significance | Breast and/or ovarian cancer | 2020-03-25 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000198223 | SCV002057305 | likely benign | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000198223 | SCV004017908 | benign | Peutz-Jeghers syndrome | 2023-04-12 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Prevention |
RCV003407603 | SCV004112158 | uncertain significance | STK11-related disorder | 2023-12-05 | no assertion criteria provided | clinical testing | The STK11 c.1038C>T variant is not predicted to result in an amino acid change (p.=). Based on available splicing prediction programs (Alamut Visual Plus v1.6.1) this variant is predicted to create a cryptic splice donor site; however, to date this prediction has not been proven by functional studies. This variant has been observed once in a cohort of individuals who underwent genetic counseling for risk assessment of breast, ovarian, and endometrial cancer and reported as benign/likely benign (Table 1, Carvalho et al. 2023. PubMed ID: 36977404). It is observed at an allele frequency of up to ~0.0033% in a large population database and has conflicting interpretations of benign, likely benign and uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/184026/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |