Variant: NM_002834.4(PTPN11):c.1232C>T (p.Thr411Met)

CA256755

13341 (ClinVar)

Gene: PTPN11

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: c27ba4df-7313-42a7-9172-705ba69caf5e

Approved on: 2019-12-05

Published on: 2019-12-05

HGVS expressions

NM_002834.4:c.1232C>T
NM_002834.4(PTPN11):c.1232C>T (p.Thr411Met)
NM_002834.3:c.1232C>T
NM_080601.1:c.1232C>T
NM_001330437.1:c.1244C>T
NM_080601.2:c.1232C>T
NM_001330437.2:c.1244C>T
NM_001374625.1:c.1229C>T
NM_002834.5:c.1232C>T
NM_080601.3:c.1232C>T
ENST00000351677.6:c.1232C>T
ENST00000392597.5:c.1232C>T
ENST00000635625.1:n.1244C>T
ENST00000635652.1:n.245C>T
NC_000012.12:g.112486482C>T
CM000674.2:g.112486482C>T
NC_000012.11:g.112924286C>T
CM000674.1:g.112924286C>T
NC_000012.10:g.111408669C>T
NG_007459.1:g.72751C>T

Uncertain Significance

• Met criteria codes: PP2

Expert Panel

RASopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

RASopathy VCEP

The c.1232C>T (p.Thr411Met) variant PTPN11 is present in 0.003% (3/113264) non-Finnish European alleles in gnomAD. 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). Observed cases from laboratories and publications lack sufficient clinical phenotypic information to support or refute pathogenicity (Institut Universitaire d'Hématologie internal data; Institute of Human Genetics, University Hospital Magdeburg, Germany internal data; PMID:15384080). In summary, the clinical significance of the p.Thr411Met variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2.

Met criteria codes

• 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).