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NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser) AND LEOPARD syndrome 1

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 1, 2023
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:
RCV001197417.12

Allele description [Variation Report for NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)]

NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)

Gene:
PTPN11:protein tyrosine phosphatase non-receptor type 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.13
Genomic location:
Preferred name:
NM_002834.5(PTPN11):c.923A>G (p.Asn308Ser)
Other names:
p.N308S:AAT>AGT
HGVS:
  • NC_000012.12:g.112477720A>G
  • NG_007459.1:g.63989A>G
  • NM_001330437.2:c.923A>G
  • NM_001374625.1:c.920A>G
  • NM_002834.5:c.923A>GMANE SELECT
  • NM_080601.3:c.923A>G
  • NP_001317366.1:p.Asn308Ser
  • NP_001361554.1:p.Asn307Ser
  • NP_002825.3:p.Asn308Ser
  • NP_542168.1:p.Asn308Ser
  • LRG_614t1:c.923A>G
  • LRG_614:g.63989A>G
  • NC_000012.11:g.112915524A>G
  • NM_001330437.2:c.923A>G
  • NM_002834.1:c.923A>G
  • NM_002834.3:c.923A>G
  • NM_002834.4:c.923A>G
  • NM_080601.1:c.923A>G
  • Q06124:p.Asn308Ser
  • c.923A>G
  • p.(Asn308Ser)
  • p.ASN308SER
Protein change:
N307S; ASN308SER
Links:
UniProtKB: Q06124#VAR_015618; OMIM: 176876.0004; dbSNP: rs121918455
NCBI 1000 Genomes Browser:
rs121918455
Molecular consequence:
  • NM_001330437.2:c.923A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374625.1:c.920A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002834.5:c.923A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080601.3:c.923A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
LEOPARD syndrome 1 (LPRD1)
Synonyms:
LENTIGINOSIS, CARDIOMYOPATHIC; MULTIPLE LENTIGINES SYNDROME
Identifiers:
MONDO: MONDO:0100082; MedGen: C4551484; Orphanet: 500; OMIM: 151100

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001368151Centre for Mendelian Genomics, University Medical Centre Ljubljana
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 1, 2016) 		unknownclinical testing

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

SCV004175774Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 1, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001368151.2

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

Description

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM1,PM2,PP2,PP4.

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004175774.1

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

Description

The missense c.923A>G (p.Asn308Ser) variant in PTPN11 gene has been reported in heterozygous state in multiple individuals affected with PTPN11-related disorders (Digilio et al., 2013; Lepri et al., 2014; Loddo et al., 2015). It has also been observed to segregate with disease in related individuals (Digilio et al., 2013). Functional studies demonstrate a damaging effect showing that the variant impacts substrate specificity of the catalytic site (Keilhack et al., 2005). This variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). The amino acid change p.Asn308Ser in PTPN11 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 308 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Pathogenic

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

Last Updated: Nov 3, 2024