Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000034327 | SCV000058288 | pathogenic | not provided | 2013-03-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000034327 | SCV000208985 | pathogenic | not provided | 2021-04-21 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16263833, 18470943, 24803665, 31978184) |
| Ambry Genetics | RCV002408501 | SCV002717198 | likely pathogenic | Cardiovascular phenotype | 2020-03-27 | criteria provided, single submitter | clinical testing | The p.G60C variant (also known as c.178G>T), located in coding exon 3 of the PTPN11 gene, results from a G to T substitution at nucleotide position 178. The glycine at codon 60 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant was reported in one individual with Noonan syndrome, severe pulmonary valve stenosis, and chronic myelomonocytic leukaemia (La Starza R et al. Leukemia, 2007 Apr;21:830-3). It was also identified in an individual undergoing growth hormone treatment; however, clinical details were limited (Limal JM et al. J. Clin. Endocrinol. Metab., 2006 Jan;91:300-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. A known disease-causing mutation, p.G60A, has been described in the same codon (Tartaglia M et al. Am. J. Hum. Genet., 2002 Jun;70:1555-63; Tartaglia M et al. Am. J. Hum. Genet., 2006 Feb;78:279-90; Bertola DR et al. Genet. Test., 2006;10:186-91; Jongmans MC et al. Eur. J. Hum. Genet., 2011 Aug;19:870-4; Atik T et al. Indian J Pediatr, 2016 Jun;83:517-21). Based on the majority of available evidence to date, the p.G60C variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV002514147 | SCV003442103 | pathogenic | RASopathy | 2024-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 60 of the PTPN11 protein (p.Gly60Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Noonan syndrome (PMID: 16263833, 21407260). ClinVar contains an entry for this variant (Variation ID: 41442). 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%. This variant disrupts the p.Gly60 amino acid residue in PTPN11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11992261, 17020470, 18328949, 24039098, 26817465). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Clinical Genetics Laboratory, |
RCV000034327 | SCV005197293 | pathogenic | not provided | 2023-12-06 | criteria provided, single submitter | clinical testing |