Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647480 | SCV000769276 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2019-06-04 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with leucine at codon 755 of the ALK protein (p.His755Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is present in population databases (rs375480327, ExAC 0.002%). This variant has not been reported in the literature in individuals with ALK-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV003352967 | SCV004073487 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | The p.H755L variant (also known as c.2264A>T), located in coding exon 13 of the ALK gene, results from an A to T substitution at nucleotide position 2264. The histidine at codon 755 is replaced by leucine, 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. |