Submissions for variant NM_002834.5(PTPN11):c.526-8C>A

gnomAD frequency: 0.00064  dbSNP: rs184804143

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000033495	SCV000616445	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.526-8C>A variant in the PTPN11 gene is 0.079% (65/66646) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
GeneDx	RCV000033495	SCV000057400	poly	RASopathy		criteria provided, single submitter	clinical testing	Converted during submission to Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037650	SCV000061312	likely benign	not specified	2015-05-18	criteria provided, single submitter	clinical testing	c.526-8C>A in intron 4 of PTPN11: This variant is not expected to have clinical significance because a change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. Furthermore, sp lice variants are not a known mechanism of disease for Noonan syndrome. It has a lso been identified in 0.1% (65/66646) of European chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs184804143).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000033495	SCV000261492	benign	RASopathy	2025-02-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000037650	SCV000309211	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000037650	SCV000342020	benign	not specified	2016-05-31	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000430276	SCV000511203	likely benign	not provided	2016-10-17	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Illumina Laboratory Services, Illumina	RCV001109476	SCV001266818	benign	Metachondromatosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001109477	SCV001266819	benign	LEOPARD syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001109478	SCV001266820	uncertain significance	Noonan syndrome 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001109477	SCV001368527	benign	LEOPARD syndrome 1	2019-03-08	criteria provided, single submitter	clinical testing	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813213	SCV002060593	benign	Noonan syndrome and Noonan-related syndrome	2020-04-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000037650	SCV002068766	likely benign	not specified	2020-09-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000430276	SCV004131964	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	PTPN11: BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000430276	SCV004564891	likely benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030388	SCV000053057	benign	Noonan syndrome	2013-10-11	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000430276	SCV001800601	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000430276	SCV001807381	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037650	SCV001925846	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000430276	SCV001955664	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000430276	SCV001965204	likely benign	not provided		no assertion criteria provided	clinical testing