ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.946C>A (p.Pro316Thr)

gnomAD frequency: 0.00001  dbSNP: rs1254406721
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800887 SCV000940630 uncertain significance Neuroblastoma, susceptibility to, 3 2022-07-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with ALK-related conditions. This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 316 of the ALK protein (p.Pro316Thr). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 646572). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV002370115 SCV002688333 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-15 criteria provided, single submitter clinical testing The p.P316T variant (also known as c.946C>A), located in coding exon 3 of the ALK gene, results from a C to A substitution at nucleotide position 946. The proline at codon 316 is replaced by threonine, 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.

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