ClinVar Miner

Submissions for variant NM_002834.4(PTPN11):c.558G>T (p.Arg186=) (rs200920312)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000519311 SCV000616446 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.558G>T (p.Arg186=) variant in the PTPN11 gene is 0.231% (49/16504) of South Asian 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)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154804 SCV000204484 likely benign not specified 2012-03-19 criteria provided, single submitter clinical testing p.Arg186Arg in Exon 05 of PTPN11: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence. It has been identified in 1/3738 African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS;).
PreventionGenetics,PreventionGenetics RCV000154804 SCV000309213 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000154804 SCV000514319 benign not specified 2015-07-28 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.
Integrated Genetics/Laboratory Corporation of America RCV000586177 SCV000698079 benign not provided 2016-10-31 criteria provided, single submitter clinical testing Variant summary: The PTPN11 c.558G>T (p.Arg186Arg) variant causes a synonymous change involving a non-conserved nucleotide with 3/5 splice prediction tools predict no significant impact on normal splicing and no alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 60/121366 (1/2022, 1 homozygote), predominantly observed in the South Asian cohort, 49/16504 (1/336, 1 homozygote), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic PTPN11 variant of 1/16000. Therefore, suggesting the variant is a common polymorphism found in population(s) of South Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. However, multiple clinical diagnostic laboratories/databases cite the variant as "likely benign." Therefore, the variant of interest has been classified as Benign.
Ambry Genetics RCV000617423 SCV000740201 likely benign Cardiovascular phenotype 2017-02-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign,In silico models in agreement (benign)
Invitae RCV000586177 SCV000776907 benign not provided 2019-01-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718046 SCV000848907 likely benign History of neurodevelopmental disorder 2017-02-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign,In silico models in agreement (benign)

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