ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.663A>G (p.Ile221Met)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Endocrinology Unit / Unidade de Endocrinologia Genetica - LIM25, Universidade de Sao Paulo (USP) RCV001779145 SCV002016192 likely pathogenic Proportionate short stature 2021-11-17 criteria provided, single submitter clinical testing De novo heterozygous variant, in a conserved region in a gene with few variants, absent in public databases: PM1, PM2, PM5, PM6, PP2, PP3
Mendelics RCV002246254 SCV002518946 pathogenic LEOPARD syndrome 1 2022-05-04 criteria provided, single submitter clinical testing
3billion RCV003152757 SCV003841483 likely pathogenic Noonan syndrome 1 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.70; 3Cnet: 0.88). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000981584). A different missense change at the same codon (p.Ile221Val) has been reported to be associated with PTPN11-related disorder (ClinVar ID: VCV000181498 / PMID: 24451042). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Service de Génétique Moléculaire, Hôpital Robert Debré RCV001261107 SCV001438514 uncertain significance Noonan syndrome no assertion criteria provided clinical testing

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