ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.762ACA[4] (p.Gln257dup) (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).
Invitae RCV000033498 SCV001558617 uncertain significance Rasopathy 2020-01-27 criteria provided, single submitter clinical testing This variant, c.768_770dup, results in the insertion of 1 amino acid(s) to the PTPN11 protein (p.Gln257dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Noonan syndrome (PMID: 22465605). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
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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