ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1449T>G (p.Gly483=) (rs143238917)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV001030074 SCV001192862 likely benign Rasopathy 2019-08-19 reviewed by expert panel curation The filtering allele frequency of the c.1449T>G (p.Gly483=) variant in the PTPN11 gene is .01% (13/129134 with CI 95%) of non-Finnish European alleles in gnomAD (BS1 not met). Computational prediction tools and conservation analysis suggest that the p.Gly483= variant does not impact the protein or splicing (BP4). This is a synonymous variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). This variant has been observed with another pathogenic variant in PTPN11 for a fully penetrant dominant gene/disorder (BP2; VCV000013326.4; Laboratory for Molecular Medicine internal data). This variant has been observed in many individuals with varying clinical presentations that lack clear associations with a RASopathy (VCV000013326.4; VCV000045358.1). In summary, the clinical significance of the p.Gly483= variant is likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP2, BP4, BP7.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037613 SCV000061275 likely benign not specified 2008-03-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726049 SCV000341504 uncertain significance not provided 2016-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000404739 SCV000376332 likely benign LEOPARD syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000297146 SCV000376333 uncertain significance Noonan syndrome 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000335748 SCV000376334 likely benign Metachondromatosis 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics RCV000618095 SCV000736857 likely benign Cardiovascular phenotype 2017-06-16 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001030074 SCV001615069 likely benign Rasopathy 2020-11-27 criteria provided, single submitter clinical testing
GeneDx RCV000726049 SCV001842080 likely benign not provided 2021-02-11 criteria provided, single submitter clinical testing

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