ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.3338G>A (p.Arg1113Gln)

gnomAD frequency: 0.00005  dbSNP: rs199987354
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566636 SCV000672469 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-10 criteria provided, single submitter clinical testing The p.R1113Q variant (also known as c.3338G>A), located in coding exon 20 of the ALK gene, results from a G to A substitution at nucleotide position 3338. The arginine at codon 1113 is replaced by glutamine, an amino acid with highly similar 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 RCV000647454 SCV000769250 likely benign Neuroblastoma, susceptibility to, 3 2024-01-28 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000566636 SCV002528474 likely benign Hereditary cancer-predisposing syndrome 2021-05-06 criteria provided, single submitter curation
Baylor Genetics RCV000647454 SCV004198601 uncertain significance Neuroblastoma, susceptibility to, 3 2024-03-29 criteria provided, single submitter clinical testing
GeneDx RCV001354522 SCV005325476 uncertain significance not provided 2024-02-21 criteria provided, single submitter clinical testing 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
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354522 SCV001549163 uncertain significance not provided no assertion criteria provided clinical testing The ALK p.R1113Q variant was not identified in the literature but was identified in dbSNP (ID: rs199987354) and ClinVar (classified as uncertain significance by Ambry Genetics and as likely benign by Invitae). The variant was identified in control databases in 14 of 282560 chromosomes at a frequency of 0.00004955, and was observed at the highest frequency in the Ashkenazi Jewish population in 11 of 10368 chromosomes (freq: 0.001061) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.R1113 residue is conserved in mammals and more distantly related organisms, and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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