ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3664G>C (p.Ala1222Pro)

dbSNP: rs1060500207
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468673 SCV000541817 uncertain significance Neuroblastoma, susceptibility to, 3 2023-06-02 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 404310). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1222 of the ALK protein (p.Ala1222Pro).
Ambry Genetics RCV001020833 SCV001182365 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-12 criteria provided, single submitter clinical testing The p.A1222P variant (also known as c.3664G>C), located in coding exon 24 of the ALK gene, results from a G to C substitution at nucleotide position 3664. The alanine at codon 1222 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. 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.

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