ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.526-17T>C

gnomAD frequency: 0.00096  dbSNP: rs375184329
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000243321 SCV000309209 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000243321 SCV000514317 benign not specified 2015-07-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000243321 SCV001362747 benign not specified 2019-09-09 criteria provided, single submitter clinical testing Variant summary: PTPN11 c.526-17T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00044 in 250878 control chromosomes, predominantly at a frequency of 0.0031 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 49 fold of the estimated maximal expected allele frequency for a pathogenic variant in PTPN11 causing Noonan Syndrome and Related Conditions phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.526-17T>C in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV002058126 SCV002338108 benign RASopathy 2024-01-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002503939 SCV002810254 likely benign Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2021-09-14 criteria provided, single submitter clinical testing

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