ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1366G>A (p.Val456Met)

gnomAD frequency: 0.00001  dbSNP: rs397516796
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037610 SCV000061271 uncertain significance not specified 2010-10-25 criteria provided, single submitter clinical testing The Val456Met variant in PTPN11 has not previously been reported in the literatu re or public databases, and it has not been previously identified by our laborat ory. Therefore, the clinical significance of this variant cannot be determined a t this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV000461820 SCV000549992 uncertain significance RASopathy 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 456 of the PTPN11 protein (p.Val456Met). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PTPN11-related conditions. ClinVar contains an entry for this variant (Variation ID: 44597). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PTPN11 protein function with a positive predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV005007951 SCV005632301 uncertain significance Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2024-03-06 criteria provided, single submitter clinical testing

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