Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000691079 | SCV000818819 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2022-10-08 | 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 C25"). ClinVar contains an entry for this variant (Variation ID: 570258). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1105 of the ALK protein (p.Ile1105Val). |
Ambry Genetics | RCV001019907 | SCV001181321 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-26 | criteria provided, single submitter | clinical testing | The p.I1105V variant (also known as c.3313A>G), located in coding exon 20 of the ALK gene, results from an A to G substitution at nucleotide position 3313. The isoleucine at codon 1105 is replaced by valine, an amino acid with highly similar properties. This alteration has been observed in at least one individual with a personal history that is consistent with ALK-related neuroblastic tumor susceptibility-related disease (Ambry internal data). This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. 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. |
Gene |
RCV003322808 | SCV004028324 | uncertain significance | not provided | 2023-02-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV000691079 | SCV004190402 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-06-28 | criteria provided, single submitter | clinical testing |