Submissions for variant NM_000455.5(STK11):c.612C>G (p.Phe204Leu)

dbSNP: rs774100153

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001178798	SCV001343319	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-28	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with leucine at codon 204 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 performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/207118 chromosomes 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	RCV002555495	SCV003523583	uncertain significance	Peutz-Jeghers syndrome	2023-06-17	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. 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. ClinVar contains an entry for this variant (Variation ID: 920208). This missense change has been observed in individual(s) with breast cancer (PMID: 28580595). This variant is present in population databases (rs774100153, gnomAD 0.002%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 204 of the STK11 protein (p.Phe204Leu).
All of Us Research Program, National Institutes of Health	RCV002555495	SCV004816383	uncertain significance	Peutz-Jeghers syndrome	2023-08-28	criteria provided, single submitter	clinical testing	This missense variant replaces phenylalanine with leucine at codon 204 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/207118 chromosomes 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.
Ambry Genetics	RCV001178798	SCV005035513	uncertain significance	Hereditary cancer-predisposing syndrome	2023-09-15	criteria provided, single submitter	clinical testing	The p.F204L variant (also known as c.612C>G), located in coding exon 5 of the STK11 gene, results from a C to G substitution at nucleotide position 612. The phenylalanine at codon 204 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly 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.