ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.4012G>T (p.Val1338Phe)

dbSNP: rs1573084680
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000798662 SCV000938288 uncertain significance Neuroblastoma, susceptibility to, 3 2022-04-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1338 of the ALK protein (p.Val1338Phe). 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: 644691). 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: "Probably Damaging"; 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 RCV001021660 SCV001183305 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-26 criteria provided, single submitter clinical testing The p.V1338F variant (also known as c.4012G>T), located in coding exon 27 of the ALK gene, results from a G to T substitution at nucleotide position 4012. The valine at codon 1338 is replaced by phenylalanine, 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.

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