ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3992C>A (p.Pro1331His)

gnomAD frequency: 0.00001  dbSNP: rs370364694
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001915023 SCV002177302 uncertain significance Neuroblastoma, susceptibility to, 3 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 1331 of the ALK protein (p.Pro1331His). This variant is not present in population databases (gnomAD no frequency). 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: 1398383). 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 RCV002370474 SCV002625013 uncertain significance Hereditary cancer-predisposing syndrome 2024-02-08 criteria provided, single submitter clinical testing The p.P1331H variant (also known as c.3992C>A), located in coding exon 27 of the ALK gene, results from a C to A substitution at nucleotide position 3992. The proline at codon 1331 is replaced by histidine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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