ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3380T>C (p.Phe1127Ser)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002280415 SCV002568500 uncertain significance not provided 2022-02-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002454610 SCV002616871 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-15 criteria provided, single submitter clinical testing The p.F1127S variant (also known as c.3380T>C), located in coding exon 21 of the ALK gene, results from a T to C substitution at nucleotide position 3380. The phenylalanine at codon 1127 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003096312 SCV003451594 uncertain significance Neuroblastoma, susceptibility to, 3 2021-12-17 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1127 of the ALK protein (p.Phe1127Ser).

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