Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
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, |
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, |
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, |
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 |
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. |