ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.762ACA[4] (p.Gln257dup)

dbSNP: rs397507524
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033498 SCV000057403 pathogenic RASopathy 2013-02-12 criteria provided, single submitter clinical testing The c.770_771insACA mutation results in the duplication of codon Glutamine 257. The normal sequence with the bases that are inserted in braces is: AACA{ACA}GGAG.This mutation has been reported as insCAA(Gln256) in association with a PTPN11-related phenotype (Ezquieta et al., 2012). This mutation is reported to have segregated with the phenotype in the family and was absent from 700 control alleles. The variant is found in NOONAN panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000033498 SCV001558617 pathogenic RASopathy 2022-08-09 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects PTPN11 function (PMID: 32112654). This variant is also known as c.766insCAA. This variant has been observed in individuals with Noonan syndrome (PMID: 22465605, 32112654). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.768_770dup, results in the insertion of 1 amino acid(s) of the PTPN11 protein (p.Gln257dup), but otherwise preserves the integrity of the reading frame.
Department of Human Genetics, University Hospital Magdeburg RCV000991103 SCV001132048 likely pathogenic Noonan syndrome 1 2019-12-19 no assertion criteria provided clinical testing We found the variant in the the index patient, his similarly affected brother and his mildly affected mother. The variant is not reported in gnomAD. The variant has been published (Collazo et al, 2012). Functional experiments show an activating effect.

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