Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000519311 | SCV000616446 | benign | RASopathy | 2017-04-18 | reviewed by expert panel | curation | The filtering allele frequency of the c.558G>T (p.Arg186=) variant in the PTPN11 gene is 0.231% (49/16504) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) |
Laboratory for Molecular Medicine, |
RCV000154804 | SCV000204484 | likely benign | not specified | 2012-03-19 | criteria provided, single submitter | clinical testing | p.Arg186Arg in Exon 05 of PTPN11: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence. It has been identified in 1/3738 African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS;). |
Prevention |
RCV000154804 | SCV000309213 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Gene |
RCV000154804 | SCV000514319 | benign | not specified | 2015-07-28 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586177 | SCV000698079 | benign | not provided | 2016-10-31 | criteria provided, single submitter | clinical testing | Variant summary: The PTPN11 c.558G>T (p.Arg186Arg) variant causes a synonymous change involving a non-conserved nucleotide with 3/5 splice prediction tools predict no significant impact on normal splicing and no alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 60/121366 (1/2022, 1 homozygote), predominantly observed in the South Asian cohort, 49/16504 (1/336, 1 homozygote), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic PTPN11 variant of 1/16000. Therefore, suggesting the variant is a common polymorphism found in population(s) of South Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. However, multiple clinical diagnostic laboratories/databases cite the variant as "likely benign." Therefore, the variant of interest has been classified as Benign. |
Ambry Genetics | RCV000617423 | SCV000740201 | likely benign | Cardiovascular phenotype | 2017-02-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV000519311 | SCV000776907 | benign | RASopathy | 2024-01-29 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000154804 | SCV001159460 | benign | not specified | 2019-05-18 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001109479 | SCV001266821 | benign | Metachondromatosis | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Illumina Laboratory Services, |
RCV001109480 | SCV001266822 | likely benign | Noonan syndrome 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Illumina Laboratory Services, |
RCV001109481 | SCV001266823 | benign | LEOPARD syndrome 1 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Genome Diagnostics Laboratory, |
RCV001813400 | SCV002060596 | likely benign | Noonan syndrome and Noonan-related syndrome | 2020-12-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000154804 | SCV002066638 | likely benign | not specified | 2020-05-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002498744 | SCV002809665 | likely benign | Noonan syndrome 1; Juvenile myelomonocytic leukemia; Metachondromatosis; LEOPARD syndrome 1 | 2022-04-25 | criteria provided, single submitter | clinical testing | |
KCCC/NGS Laboratory, |
RCV003315942 | SCV004017219 | benign | Juvenile myelomonocytic leukemia | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000586177 | SCV004131966 | likely benign | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | PTPN11: BP4, BP7, BS1 |