Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000791984 | SCV000931255 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 44 of the ALK protein (p.Leu44Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 639239). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Gene |
RCV001776001 | SCV002013357 | uncertain significance | not provided | 2021-05-06 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002386373 | SCV002694838 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-12 | criteria provided, single submitter | clinical testing | The p.L44R variant (also known as c.131T>G), located in coding exon 1 of the ALK gene, results from a T to G substitution at nucleotide position 131. The leucine at codon 44 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV000791984 | SCV005649296 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-03-05 | criteria provided, single submitter | clinical testing |