Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647417 | SCV000769213 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 505 of the ALK protein (p.Thr505Ile). This variant is present in population databases (rs751321667, gnomAD 0.004%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 538214). This variant has not been reported in the literature in individuals affected with ALK-related conditions. |
Ambry Genetics | RCV002388115 | SCV002704772 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-15 | criteria provided, single submitter | clinical testing | The p.T505I variant (also known as c.1514C>T), located in coding exon 7 of the ALK gene, results from a C to T substitution at nucleotide position 1514. The threonine at codon 505 is replaced by isoleucine, 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. |