Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000799861 | SCV000939543 | uncertain significance | Neuroblastoma, susceptibility to, 3 | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1404 of the ALK protein (p.Leu1404Pro). This variant is present in population databases (rs377129811, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast cancer (PMID: 28202063). ClinVar contains an entry for this variant (Variation ID: 645717). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Gene |
RCV003442083 | SCV004168576 | likely benign | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with a personal and/or family history of breast cancer (Jalkh et al., 2017); This variant is associated with the following publications: (PMID: 28202063) |