ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.1473A>T (p.Gln491His)

dbSNP: rs1573227409
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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 RCV001967041 SCV002255294 uncertain significance Neuroblastoma, susceptibility to, 3 2023-06-23 criteria provided, single submitter clinical testing 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. This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 491 of the ALK protein (p.Gln491His). 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: 1471963).
Ambry Genetics RCV002388964 SCV002701072 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-07 criteria provided, single submitter clinical testing The p.Q491H variant (also known as c.1473A>T), located in coding exon 7 of the ALK gene, results from an A to T substitution at nucleotide position 1473. The glutamine at codon 491 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
GeneDx RCV004779232 SCV005388994 uncertain significance not provided 2024-03-04 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports 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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