ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3595A>C (p.Met1199Leu)

dbSNP: rs1400239417
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000531281 SCV000648704 uncertain significance Neuroblastoma, susceptibility to, 3 2025-01-08 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1199 of the ALK protein (p.Met1199Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with medulloblastoma (PMID: 27179218). ClinVar contains an entry for this variant (Variation ID: 470837). 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. 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.
Ambry Genetics RCV001020679 SCV001182189 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-27 criteria provided, single submitter clinical testing The p.M1199L variant (also known as c.3595A>C), located in coding exon 23 of the ALK gene, results from an A to C substitution at nucleotide position 3595. The methionine at codon 1199 is replaced by leucine, an amino acid with highly similar properties. An alteration resulting in the same amino acid change, p.M1199L (c.3595A>T), has been reported in a patient with medulloblastoma (Trubicka J et al. Folia Neuropathol, 2016;54:23-30). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000531281 SCV004191749 uncertain significance Neuroblastoma, susceptibility to, 3 2023-09-01 criteria provided, single submitter clinical testing

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