Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570349 | SCV000672484 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-29 | criteria provided, single submitter | clinical testing | The p.R1214C variant (also known as c.3640C>T), located in coding exon 23 of the ALK gene, results from a C to T substitution at nucleotide position 3640. The arginine at codon 1214 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Invitae | RCV002530324 | SCV003515141 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-10-07 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 485083). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs758172315, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1214 of the ALK protein (p.Arg1214Cys). |
Baylor Genetics | RCV002530324 | SCV004190547 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-06-14 | criteria provided, single submitter | clinical testing |