ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3548T>C (p.Ile1183Thr)

gnomAD frequency: 0.00001  dbSNP: rs1002995598
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000796826 SCV000936354 uncertain significance Neuroblastoma, susceptibility to, 3 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1183 of the ALK protein (p.Ile1183Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with neuroblastoma (PMID: 25517749). ClinVar contains an entry for this variant (Variation ID: 643179). 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. Experimental studies have shown that this missense change does not substantially affect ALK function (PMID: 25517749). 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 RCV001020573 SCV001182071 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-10 criteria provided, single submitter clinical testing The p.I1183T variant (also known as c.3548T>C), located in coding exon 23 of the ALK gene, results from a T to C substitution at nucleotide position 3548. The isoleucine at codon 1183 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003317370 SCV004021845 uncertain significance not provided 2023-01-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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