Submissions for variant NM_000455.5(STK11):c.1262_1263delinsAT (p.Ser421Asn)

dbSNP: rs1555740261

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000560077	SCV000629087	uncertain significance	Peutz-Jeghers syndrome	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 421 of the STK11 protein (p.Ser421Asn). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 458030). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics	RCV000562727	SCV000672345	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-18	criteria provided, single submitter	clinical testing	The c.1262_1263delGCinsAT variant (also known as p.S421N), located in coding exon 9 of the STK11 gene, results from a deletion of GC and insertion of AT between nucleotide positions 1262 and 1263. This results in the substitution of the serine residue for an asparagine residue at codon 421, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000562727	SCV001734271	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-26	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 421 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). 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.
Genome-Nilou Lab	RCV000560077	SCV002058001	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002476112	SCV002774742	uncertain significance	not provided	2021-06-22	criteria provided, single submitter	clinical testing