Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193822 | SCV001362957 | uncertain significance | not specified | 2019-12-23 | criteria provided, single submitter | clinical testing | Variant summary: ALK c.2569C>T (p.His857Tyr) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251484 control chromosomes. 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.2569C>T in individuals affected with Neuroblastoma and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV001232680 | SCV001405246 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 857 of the ALK protein (p.His857Tyr). This variant is present in population databases (rs754393402, gnomAD 0.007%). 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: 929023). 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. |
| Ambry Genetics | RCV002451404 | SCV002739524 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-18 | criteria provided, single submitter | clinical testing | The p.H857Y variant (also known as c.2569C>T), located in coding exon 15 of the ALK gene, results from a C to T substitution at nucleotide position 2569. The histidine at codon 857 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |