Submissions for variant NM_000455.5(STK11):c.38C>T (p.Thr13Met)

dbSNP: rs1599914790

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000820072	SCV000960766	uncertain significance	Peutz-Jeghers syndrome	2023-12-12	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 13 of the STK11 protein (p.Thr13Met). This variant is not present in population databases (gnomAD no frequency). 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: 662432). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on STK11 protein function. 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	RCV001181154	SCV001346248	uncertain significance	Hereditary cancer-predisposing syndrome	2021-03-22	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with methionine at codon 13 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.
Genome-Nilou Lab	RCV000820072	SCV002057715	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001181154	SCV002620942	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-08	criteria provided, single submitter	clinical testing	The p.T13M variant (also known as c.38C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 38. The threonine at codon 13 is replaced by methionine, an amino acid with similar properties. This alteration was not observed in 53 unselected male breast cancer patients and was observed with an allele frequency of 0.0001 in 12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 10;9:4083). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.