ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.4619C>G (p.Thr1540Ser)

gnomAD frequency: 0.00002  dbSNP: rs1215255332
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001982301 SCV002215238 uncertain significance Neuroblastoma, susceptibility to, 3 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1540 of the ALK protein (p.Thr1540Ser). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 1433627). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine 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.
Sema4, Sema4 RCV002258330 SCV002528515 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-02 criteria provided, single submitter curation
Ambry Genetics RCV002258330 SCV002633389 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-19 criteria provided, single submitter clinical testing The p.T1540S variant (also known as c.4619C>G), located in coding exon 29 of the ALK gene, results from a C to G substitution at nucleotide position 4619. The threonine at codon 1540 is replaced by serine, an amino acid with 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.
Baylor Genetics RCV001982301 SCV004198723 uncertain significance Neuroblastoma, susceptibility to, 3 2023-09-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001982301 SCV005653607 uncertain significance Neuroblastoma, susceptibility to, 3 2024-04-22 criteria provided, single submitter clinical testing

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