Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001891129 | SCV002164992 | uncertain significance | not provided | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 352 of the DLL3 protein (p.Lys352Asn). This variant is present in population databases (rs376526613, gnomAD 0.008%). 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: 1390694). 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: "Possibly 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. |
ARUP Laboratories, |
RCV003617946 | SCV004564183 | uncertain significance | Spondylocostal dysostosis 1, autosomal recessive | 2023-09-06 | criteria provided, single submitter | clinical testing | The DLL3 c.1056G>T; p.Lys352Asn variant (rs376526613), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1390694). This variant is observed in the general population with an overall allele frequency of 0.004% (12/282728 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.461). Due to limited information, the clinical significance of this variant is uncertain at this time. |
Ambry Genetics | RCV004975788 | SCV005567597 | uncertain significance | Inborn genetic diseases | 2024-10-01 | criteria provided, single submitter | clinical testing | The c.1056G>T (p.K352N) alteration is located in exon 6 (coding exon 6) of the DLL3 gene. This alteration results from a G to T substitution at nucleotide position 1056, causing the lysine (K) at amino acid position 352 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |