Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002026267 | SCV002303131 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-06-28 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ALK-related conditions. This sequence change replaces histidine with glutamine at codon 514 of the ALK protein (p.His514Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. |
Ambry Genetics | RCV003161229 | SCV003861070 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-04 | criteria provided, single submitter | clinical testing | The p.H514Q variant (also known as c.1542C>A), located in coding exon 7 of the ALK gene, results from a C to A substitution at nucleotide position 1542. The histidine at codon 514 is replaced by glutamine, 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. |