ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.1048T>G (p.Ser350Ala)

gnomAD frequency: 0.00001  dbSNP: rs146571700
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000033523 SCV000057428 likely benign not provided 2020-11-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763793 SCV000894707 uncertain significance Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV003539767 SCV004305892 uncertain significance RASopathy 2023-12-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 350 of the PTPN11 protein (p.Ser350Ala). This variant is present in population databases (rs146571700, gnomAD 0.003%). 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: 40540). 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.
Ambry Genetics RCV004018712 SCV004934876 uncertain significance Cardiovascular phenotype 2020-01-23 criteria provided, single submitter clinical testing The c.1048T>G (p.S350A) alteration is located in exon 9 (coding exon 9) of the PTPN11 gene. This alteration results from a T to G substitution at nucleotide position 1048, causing the serine (S) at amino acid position 350 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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