Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
St. |
RCV000761126 | SCV000891042 | uncertain significance | Noonan syndrome | 2020-09-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001517426 | SCV001725915 | benign | RASopathy | 2023-08-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994107 | SCV004813949 | uncertain significance | not specified | 2024-02-08 | criteria provided, single submitter | clinical testing | Variant summary: PTPN11 c.15-4delT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251230 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.15-4delT in individuals affected with Noonan Syndrome/Leopard Syndrome or other PTPN11-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 620622). Based on the evidence outlined above, the variant was classified as uncertain significance. |