Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237488 | SCV001410249 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-03-16 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 963459). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1143 of the ALK protein (p.Ser1143Ile). |
Ambry Genetics | RCV002327572 | SCV002618980 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | The p.S1143I variant (also known as c.3428G>T), located in coding exon 21 of the ALK gene, results from a G to T substitution at nucleotide position 3428. The serine at codon 1143 is replaced by isoleucine, an amino acid with dissimilar 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. |