Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694546 | SCV000822997 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 240 of the ALK protein (p.Tyr240Cys). This variant is present in population databases (rs550608288, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. 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: 573005). 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 tolerated. 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, |
RCV000694546 | SCV002048839 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2020-11-10 | criteria provided, single submitter | clinical testing | The ALK c.719A>G; p.Tyr240Cys variant (rs550608288), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is reported in ClinVar (Variation ID: 573005) and is found in the South Asian population with an allele frequency of 0.04% (11/30,616 alleles) in the Genome Aggregation Database. The tyrosine at codon 240 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.016). Due to limited information, the clinical significance of the p.Tyr240Cys variant is uncertain at this time. |
Ambry Genetics | RCV002369875 | SCV002672320 | likely benign | Hereditary cancer-predisposing syndrome | 2022-06-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |