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NM_000455.5(STK11):c.577T>G (p.Ser193Ala) AND Peutz-Jeghers syndrome

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Jan 17, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000632811.11

Allele description [Variation Report for NM_000455.5(STK11):c.577T>G (p.Ser193Ala)]

NM_000455.5(STK11):c.577T>G (p.Ser193Ala)

Gene:
STK11:serine/threonine kinase 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_000455.5(STK11):c.577T>G (p.Ser193Ala)
HGVS:
  • NC_000019.10:g.1220485T>G
  • NG_007460.2:g.36079T>G
  • NM_000455.5:c.577T>GMANE SELECT
  • NP_000446.1:p.Ser193Ala
  • NP_000446.1:p.Ser193Ala
  • LRG_319t1:c.577T>G
  • LRG_319:g.36079T>G
  • LRG_319p1:p.Ser193Ala
  • NC_000019.9:g.1220484T>G
  • NM_000455.4:c.577T>G
Protein change:
S193A
Links:
dbSNP: rs1064794883
NCBI 1000 Genomes Browser:
rs1064794883
Molecular consequence:
  • NM_000455.5:c.577T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Name:
Peutz-Jeghers syndrome (PJS)
Synonyms:
POLYPOSIS, HAMARTOMATOUS INTESTINAL; POLYPS-AND-SPOTS SYNDROME; Peutz-Jeghers polyposis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008280; MeSH: D010580; MedGen: C0031269; Orphanet: 2869; OMIM: 175200

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000754006Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 17, 2024)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002057809Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jul 15, 2021)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004816374All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Dec 13, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown3not providednot provided108544not providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754006.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 193 of the STK11 protein (p.Ser193Ala). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 421064). 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. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Genome-Nilou Lab, SCV002057809.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From All of Us Research Program, National Institutes of Health, SCV004816374.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces serine with alanine at codon 193 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). 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 1/31330 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided3not providednot providednot provided

Last Updated: Oct 8, 2024