Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001802247 | SCV002049965 | uncertain significance | Spondylocostal dysostosis 1, autosomal recessive | 2021-10-21 | criteria provided, single submitter | clinical testing | The DLL3 c.1376A>T; p.Tyr459Phe variant (rs572290101), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found in the Latino population with an overall allele frequency of 0.08% (23/29584 alleles) in the Genome Aggregation Database. The tyrosine at codon 459 is moderately conserved, it occurs as a phenylalanine in multiple vertebrate species, and computational analyses predict that this variant is neutral (REVEL: 0.129). However, given the lack of clinical and functional data, the significance of the p.Tyr459Phe variant is uncertain at this time. |
| Invitae | RCV002541356 | SCV003253405 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 459 of the DLL3 protein (p.Tyr459Phe). This variant is present in population databases (rs572290101, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with DLL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1330588). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |