Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129447 | SCV000184217 | benign | Hereditary cancer-predisposing syndrome | 2022-12-20 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Invitae | RCV000200813 | SCV000254537 | likely benign | Peutz-Jeghers syndrome | 2023-12-22 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000200813 | SCV000488826 | uncertain significance | Peutz-Jeghers syndrome | 2016-06-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000590522 | SCV000566639 | likely benign | not provided | 2021-02-10 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Color Diagnostics, |
RCV000129447 | SCV000686579 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-25 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 347 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 16/244008 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000722120 | SCV000696699 | likely benign | not specified | 2018-05-08 | criteria provided, single submitter | clinical testing | Variant summary: STK11 c.1039G>A (p.Ala347Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 21.12 fold of the estimated maximal expected allele frequency for a pathogenic variant in STK11 causing Hereditary Breast and Ovarian Cancer phenotype (1.6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.1039G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000590522 | SCV001469906 | likely benign | not provided | 2021-09-02 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000200813 | SCV002057306 | uncertain significance | Peutz-Jeghers syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129447 | SCV002531621 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-04 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000722120 | SCV002761029 | uncertain significance | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000200813 | SCV004018020 | likely benign | Peutz-Jeghers syndrome | 2023-04-14 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. Homozygosity has been confirmed in one or more individuals. As homozygosity for pathogenic variants in this gene is generally assumed to result in embryonic lethality, this variant is unlikely to be pathogenic. |
All of Us Research Program, |
RCV000200813 | SCV004818964 | uncertain significance | Peutz-Jeghers syndrome | 2023-03-07 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 347 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 16/244008 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |