Submissions for variant NM_000455.5(STK11):c.128C>T (p.Ala43Val)

dbSNP: rs1555734967

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000565536	SCV000675259	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-01	criteria provided, single submitter	clinical testing	The p.A43V variant (also known as c.128C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 128. The alanine at codon 43 is replaced by valine, an amino acid with 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	RCV000820260	SCV000960966	uncertain significance	Peutz-Jeghers syndrome	2023-08-04	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 486522). 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 not expected to disrupt 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. This variant has not been reported in the literature in individuals affected with STK11-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 43 of the STK11 protein (p.Ala43Val). This variant is not present in population databases (gnomAD no frequency).
Color Diagnostics, LLC DBA Color Health	RCV000565536	SCV001358478	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-18	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 43 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). 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 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	RCV000820260	SCV002057746	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003465276	SCV004205580	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 1	2023-06-30	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000820260	SCV004816320	uncertain significance	Peutz-Jeghers syndrome	2023-03-28	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with valine at codon 43 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). 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 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.