ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3877G>A (p.Val1293Ile)

gnomAD frequency: 0.00007  dbSNP: rs1024193740
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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 RCV001071449 SCV001236755 uncertain significance Neuroblastoma, susceptibility to, 3 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1293 of the ALK protein (p.Val1293Ile). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 864298). 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.
Ambry Genetics RCV002365785 SCV002624881 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-14 criteria provided, single submitter clinical testing The p.V1293I variant (also known as c.3877G>A), located in coding exon 26 of the ALK gene, results from a G to A substitution at nucleotide position 3877. The valine at codon 1293 is replaced by isoleucine, an amino acid with highly similar properties. 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.
GeneDx RCV004783899 SCV005396054 uncertain significance not provided 2024-05-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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