Submissions for variant NM_000455.5(STK11):c.737ACA[1] (p.Asn247del)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003360631	SCV004053375	likely pathogenic	Hereditary cancer-predisposing syndrome	2023-06-22	criteria provided, single submitter	clinical testing	The c.740_742delACA variant (also known as p.N247del) is located in coding exon 6 of the STK11 gene. This variant results from an in-frame ACA deletion at nucleotide positions 740 to 742. This results in the in-frame deletion of an asparagine at codon 247. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with STK11-related disease (Ambry internal data). Based on internal structural analysis, N247del is more disruptive to the STK11 kinase domain than a nearby pathogenic variant (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position 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). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae	RCV003507502	SCV004297970	uncertain significance	Peutz-Jeghers syndrome	2023-08-11	criteria provided, single submitter	clinical testing	This variant, c.740_742del, results in the deletion of 1 amino acid(s) of the STK11 protein (p.Asn247del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 9760200). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Color Diagnostics, LLC DBA Color Health	RCV003360631	SCV004362399	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-10	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of single amino acid in the STK11 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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.