Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000647378 | SCV000769173 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-30 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 174 of the ALK protein (p.Phe174Leu). This variant is present in population databases (rs587778020, 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: 133458). 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. 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. |
Genetic Services Laboratory, |
RCV000119962 | SCV002065770 | uncertain significance | not specified | 2021-12-08 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ALK gene demonstrated a sequence change, c.522C>A, in exon 1 that results in an amino acid change, p.Phe174Leu. This sequence change has been described in the gnomAD database with a frequency of 0.007% in the non-Finnish European subpopulation (dbSNP rs587778020). The p.Phe174Leu change affects a poorly conserved amino acid residue located in a domain of the ALK protein that is not known to be functional. The p.Phe174Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with ALK-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Phe174Leu change remains unknown at this time. |
Sema4, |
RCV002258794 | SCV002528528 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-13 | criteria provided, single submitter | curation | |
Gene |
RCV003332121 | SCV004040239 | uncertain significance | not provided | 2023-03-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Identified in individuals with a history of early-onset colorectal cancer, as well as in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014; Thutkawkorapin et al., 2019); This variant is associated with the following publications: (PMID: 30809968, 24728327, 31526103) |
Ce |
RCV003332121 | SCV004144047 | uncertain significance | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000647378 | SCV004199951 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2023-08-05 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000119962 | SCV000084092 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |