Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001055086 | SCV001219452 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1349 of the ALK protein (p.Asp1349His). This variant is present in population databases (rs368744524, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 850828). 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. Experimental studies have shown that this missense change does not substantially affect ALK function (PMID: 25517749). 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 | RCV002320302 | SCV002631844 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-08 | criteria provided, single submitter | clinical testing | The p.D1349H variant (also known as c.4045G>C), located in coding exon 27 of the ALK gene, results from a G to C substitution at nucleotide position 4045. The aspartic acid at codon 1349 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |