Submissions for variant NM_000455.5(STK11):c.297T>G (p.Ile99Met)

gnomAD frequency: 0.00001  dbSNP: rs559620061

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131468	SCV000186455	uncertain significance	Hereditary cancer-predisposing syndrome	2020-09-01	criteria provided, single submitter	clinical testing	The p.I99M variant (also known as c.297T>G), located in coding exon 2 of the STK11 gene, results from a T to G substitution at nucleotide position 297. The isoleucine at codon 99 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Invitae	RCV000803794	SCV000943680	uncertain significance	Peutz-Jeghers syndrome	2023-08-24	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: 142382). This variant has not been reported in the literature in individuals affected with STK11-related conditions. This variant is present in population databases (rs559620061, gnomAD 0.01%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 99 of the STK11 protein (p.Ile99Met).
Genome-Nilou Lab	RCV000803794	SCV002057761	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV002509240	SCV002818902	uncertain significance	not provided	2023-01-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24830819, 15863673)