ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.4537G>A (p.Glu1513Lys)

gnomAD frequency: 0.00003  dbSNP: rs374733353
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000647458 SCV000769254 uncertain significance Neuroblastoma, susceptibility to, 3 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1513 of the ALK protein (p.Glu1513Lys). This variant is present in population databases (rs374733353, gnomAD 0.01%). 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: 538249). 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 disruptive. 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 RCV002331222 SCV002634152 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-21 criteria provided, single submitter clinical testing The p.E1513K variant (also known as c.4537G>A), located in coding exon 29 of the ALK gene, results from a G to A substitution at nucleotide position 4537. The glutamic acid at codon 1513 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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.
GeneDx RCV003441994 SCV004168041 uncertain significance not provided 2023-04-17 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; Observed in an individual with precocious puberty caused by ovarian Sertoli-Leydig cancer (Monroy et al., 2021); This variant is associated with the following publications: (PMID: 29273096, Monroy2021)

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