Submissions for variant NM_000455.5(STK11):c.1262GCA[1] (p.Ser422del)

dbSNP: rs587782439

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131503	SCV000186492	uncertain significance	Hereditary cancer-predisposing syndrome	2023-08-14	criteria provided, single submitter	clinical testing	The c.1265_1267delGCA variant (also known as p.S422del) is located in coding exon 9 of the STK11 gene. This variant results from an in-frame GCA deletion at nucleotide positions 1265 to 1267. This results in the in-frame deletion of a serine at codon 422. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000229523	SCV000284856	uncertain significance	Peutz-Jeghers syndrome	2024-01-30	criteria provided, single submitter	clinical testing	This variant, c.1265_1267del, results in the deletion of 1 amino acid(s) of the STK11 protein (p.Ser422del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs764027433, gnomAD 0.002%). 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: 142404). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Counsyl	RCV000229523	SCV000489193	uncertain significance	Peutz-Jeghers syndrome	2016-08-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000486911	SCV000570573	uncertain significance	not provided	2021-12-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In-frame deletion of one amino acids in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health	RCV000131503	SCV000686611	uncertain significance	Hereditary cancer-predisposing syndrome	2023-11-15	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid at codon 422 of the STK11 protein. 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 1/162716 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.
Myriad Genetics, Inc.	RCV000229523	SCV004018019	uncertain significance	Peutz-Jeghers syndrome	2023-04-14	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV000229523	SCV004819027	uncertain significance	Peutz-Jeghers syndrome	2023-12-13	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid at codon 422 of the STK11 protein. 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 1/162716 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.