Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492760 | SCV000580950 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-09-13 | criteria provided, single submitter | clinical testing | The c.159_170del12 variant (also known as p.D53_G56del) is located in coding exon 1 of the STK11 gene. This variant results from an in-frame deletion of 12 nucleotides (CCTGCTGGGGGA) at positions 159 to 170. This results in the deletion of a four residues at codons 53 to 56. Structural analysis has concluded that this alteration removes a key gylcine rich kinase motif, and thus, leads to a deleterious functional effect on the protein (Lahiry P et al. Nat. Rev. Genet., 2010 Jan;11:60-74; Ambry internal data). Further, a similar in-frame deletion of the STK11 gene, c.151_162del12, has been reported in individuals with a clinical diagnosis of Peutz-Jeghers syndrome (Resta N, Dig Liver Dis 2013 Jul; 45(7):606-11, Ambry internal data). The c.159_170del12 variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project, however this position was not covered in the ESP. This amino acid region is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV002523987 | SCV003327294 | uncertain significance | Peutz-Jeghers syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 428793). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.159_170del, results in the deletion of 4 amino acid(s) of the STK11 protein (p.Asp53_Gly56del), but otherwise preserves the integrity of the reading frame. |
| Mayo Clinic Laboratories, |
RCV000583353 | SCV000692042 | uncertain significance | not specified | no assertion criteria provided | clinical testing |