Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001243468 | SCV001416631 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-04-08 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 968355). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs774403380, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 186 of the ALK protein (p.Arg186Lys). |
Ambry Genetics | RCV002348826 | SCV002654130 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-06 | criteria provided, single submitter | clinical testing | The p.R186K variant (also known as c.557G>A), located in coding exon 1 of the ALK gene, results from a G to A substitution at nucleotide position 557. The arginine at codon 186 is replaced by lysine, an amino acid with highly 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. |