Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000603401 | SCV000712402 | likely benign | not specified | 2016-07-29 | criteria provided, single submitter | clinical testing | c.1448-5C>T in intron 12 of PTPN11: This variant is not expected to have clinica l significance because a C>T change at this position does not diverge from the s plice consensus sequence and is therefore unlikely to impact splicing. It has be en identified in 2/16512 South Asian chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs554790621). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000603401 | SCV000918103 | likely benign | not specified | 2017-09-05 | criteria provided, single submitter | clinical testing | Variant summary: c.1448-5C>T in PTPN11 gene is an intronic change that involves a non-conserved nucleotide. 5/5 programs in Alamut indicate this variant to strengthen a canonical acceptor site, however no functional studies supporting these predictions were published at the time of evaluation. The variant is present in the control population datasets of ExAC and gnomAD at frequency of 0.00002 (2/121396 and 5/246180 chrs tested, respectively), exclusively in individuals of South Asian descent (0.00016; 2/16512 and 5/30782, chrs respectively). The observed individual frequencies exceed the maximum expected allele frequency for a pathogenic variant of 0.0000625, suggesting the variant is likely to be an ethnic polymorphism. The variant of interest has not, to our knowledge, been cited by published reports or reputable databases/clinical laboratories. Taking together the variant was classified as Likely Benign until more data become available. |
| Invitae | RCV001478592 | SCV001682863 | likely benign | RASopathy | 2022-07-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002395546 | SCV002697928 | uncertain significance | Cardiovascular phenotype | 2022-01-07 | criteria provided, single submitter | clinical testing | The c.1448-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 13 in the PTPN11 gene. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |