Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001233560 | SCV001406162 | uncertain significance | Multiple endocrine neoplasia type 4 | 2022-04-13 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the CDKN1B mRNA. The next in-frame methionine is located at codon 16. This variant is present in population databases (rs758613901, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 960097). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002430000 | SCV002743965 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-03 | criteria provided, single submitter | clinical testing | The p.M1? variant (also known as c.1_15del15) is located in coding exon 1 of the CDKN1B gene and results from a deletion of 15 nucleotides at nucleotide positions 1 to15. This alters the methionine residue at the initiation codon. Variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame; however there is an alternate in-frame methionine 15 amino acids from the initiation site and the significance of the N-terminus for this protein is not well established. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |