Submissions for variant NM_000455.5(STK11):c.901C>T (p.Arg301Trp)

gnomAD frequency: 0.00002  dbSNP: rs587780012

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000115604	SCV000149513	uncertain significance	not provided	2023-10-20	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; Observed in a patient with high risk of hereditary breast and/or ovarian cancer syndrome (Shao et al., 2020); This variant is associated with the following publications: (PMID: 15863673, 31742824, 36531003)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000467481	SCV000541144	benign	Peutz-Jeghers syndrome	2024-10-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000775659	SCV000910052	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-15	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 301 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 STK11-related disorders in the literature. This variant has been identified in 1/179496 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.
Genome-Nilou Lab	RCV000467481	SCV002057870	uncertain significance	Peutz-Jeghers syndrome	2021-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000775659	SCV002683510	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-15	criteria provided, single submitter	clinical testing	The p.R301W variant (also known as c.901C>T), located in coding exon 7 of the STK11 gene, results from a C to T substitution at nucleotide position 901. The arginine at codon 301 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was identified in a cohort of 882 Chinese individuals with a personal and/or family history of breast or ovarian cancers who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health	RCV000467481	SCV004818934	uncertain significance	Peutz-Jeghers syndrome	2024-09-27	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 301 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 1/179496 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.