Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000807103 | SCV000947139 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-01-13 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 651692). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs769449619, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg1209*) in the ALK gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ALK cause disease. |
Ambry Genetics | RCV001020753 | SCV001182267 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | The p.R1209* variant (also known as c.3625C>T), located in coding exon 23 of the ALK gene, results from a C to T substitution at nucleotide position 3625. This changes the amino acid from an arginine to a stop codon within coding exon 23. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in ALK is not the mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |