Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001224447 | SCV001396639 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2021-09-20 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs752320442, ExAC 0.006%). This sequence change replaces asparagine with serine at codon 1484 of the ALK protein (p.Asn1484Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. |
Sema4, |
RCV002259094 | SCV002528509 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-16 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV002259094 | SCV002638433 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | The p.N1484S variant (also known as c.4451A>G), located in coding exon 29 of the ALK gene, results from an A to G substitution at nucleotide position 4451. The asparagine at codon 1484 is replaced by serine, 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. |