Submissions for variant NM_000455.5(STK11):c.1162A>C (p.Lys388Gln)

dbSNP: rs878853983

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001182798	SCV001348387	uncertain significance	Hereditary cancer-predisposing syndrome	2022-02-08	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamine at codon 388 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 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.
Invitae	RCV001321488	SCV001512320	uncertain significance	Peutz-Jeghers syndrome	2022-01-27	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt STK11 protein function. ClinVar contains an entry for this variant (Variation ID: 922618). 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 sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 388 of the STK11 protein (p.Lys388Gln).
Genome-Nilou Lab	RCV001321488	SCV002057949	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001182798	SCV002622234	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-29	criteria provided, single submitter	clinical testing	The p.K388Q variant (also known as c.1162A>C), located in coding exon 9 of the STK11 gene, results from an A to C substitution at nucleotide position 1162. The lysine at codon 388 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.