ClinVar Miner

Submissions for variant NM_002834.5(PTPN11):c.824A>C (p.Asn275Thr)

gnomAD frequency: 0.00003  dbSNP: rs397507528
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001109482 SCV001266824 benign Metachondromatosis 2018-03-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV001109483 SCV001266825 benign LEOPARD syndrome 1 2018-03-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV001111779 SCV001269370 uncertain significance Noonan syndrome 1 2018-04-09 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001264525 SCV001442725 uncertain significance not specified 2020-10-01 criteria provided, single submitter clinical testing Variant summary: PTPN11 c.824A>C (p.Asn275Thr) results in a non-conservative amino acid change located in the PTP type protein phosphatase (IPR000242) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-05 in 246238 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PTPN11 causing Noonan Syndrome (4.1e-05 vs 6.3e-05), allowing no conclusion about variant significance. c.824A>C has been reported in the literature (Konstantinidis_2015). This report however, does not provide unequivocal conclusions about association of the variant with Noonan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as benign or uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001294974 SCV001483874 uncertain significance RASopathy 2023-09-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 275 of the PTPN11 protein (p.Asn275Thr). This variant is present in population databases (rs397507528, gnomAD 0.007%). 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: 40524). 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. 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 RCV003298038 SCV004000111 uncertain significance Cardiovascular phenotype 2019-05-20 criteria provided, single submitter clinical testing The c.824A>C (p.N275T) alteration is located in exon 7 (coding exon 7) of the PTPN11 gene. This alteration results from a A to C substitution at nucleotide position 824, causing the asparagine (N) at amino acid position 275 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.