Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_002834.4(PTPN11):c.244A>G (p.Met82Val)

CA243279

40504 (ClinVar)

Gene: PTPN11

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9a9c6639-bd78-4169-b494-17e19c0101cc

HGVS expressions

NM_002834.4:c.244A>G

NM_002834.4(PTPN11):c.244A>G (p.Met82Val)

NC_000012.12:g.112450424A>G

CM000674.2:g.112450424A>G

NC_000012.11:g.112888228A>G

CM000674.1:g.112888228A>G

NC_000012.10:g.111372611A>G

NG_007459.1:g.36693A>G

NM_002834.3:c.244A>G

NM_080601.1:c.244A>G

NM_001330437.1:c.244A>G

NM_080601.2:c.244A>G

NM_001330437.2:c.244A>G

NM_001374625.1:c.241A>G

NM_002834.5:c.244A>G

NM_080601.3:c.244A>G

ENST00000351677.6:c.244A>G

ENST00000392597.5:c.244A>G

ENST00000635625.1:n.244A>G

Uncertain Significance

PM6 BP5 PP2

PM2 PP3

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.244A>G (p.Met82Val) variant in PTPN11 was present in 0.006152% (1/16256) of African alleles in gnomAD (gnomad.broadinstitute.org). It was identified as a de novo occurrence in 1 proband (PM6; PMID: 30577886). It was also observed in a proband with features of Noonan syndrome with an alternate molecular mechanism of disease (BP5; GeneDx internal data, SCV000057386.12). The variant is located in the PTPN11 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID 29493581). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Met82Val variant in PTPN11 is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PM6, PP2, BP5.

PM6

Identified as a de novo occurrence (without maternity/paternity confirmed) in 1 proband (PM6; PMID: 30577886).

BP5

This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, ClinVar SCV000057386.11).

PP2

The variant is located in the PTPN11 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID 29493581).

PM2

Present in 0.006152% (1/16256) of African alleles in gnomAD.

PP3

Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein.

Approved on: 2020-05-28

Published on: 2020-07-01

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.