Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000492248 | SCV000580888 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-23 | criteria provided, single submitter | clinical testing | The c.151_162del12 variant (also known as p.M51_L54del) is located in coding exon 1 of the STK11 gene. This variant results from an in-frame deletion of 12 nucleotides at positions 151 to 162. This results in the deletion of four amino acids at codons 51 to 54. This variant has been observed in individuals with a personal and/or family history that is consistent with Peutz-Jeghers syndrome (Resta N, Dig Liver Dis 2013 Jul; 45(7):606-11; Ambry internal data). Additionally, structural analysis has concluded that this alteration deleteriously affects an adjacent and essential ATP binding loop, and thus, leads to a deleterious functional effect on the protein (Zeqiraj E, Science 2009 Dec;326(5960):1707-11). This amino acid region is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV003507283 | SCV004297965 | uncertain significance | Peutz-Jeghers syndrome | 2023-05-10 | 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: 428748). This variant has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 23415580). This variant is not present in population databases (gnomAD no frequency). This variant, c.151_162del, results in the deletion of 4 amino acid(s) of the STK11 protein (p.Met51_Leu54del), but otherwise preserves the integrity of the reading frame. |