ClinVar Miner

Submissions for variant NM_004304.5(ALK):c.692C>G (p.Thr231Arg)

gnomAD frequency: 0.00012  dbSNP: rs142120301
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000647423 SCV000769219 uncertain significance Neuroblastoma, susceptibility to, 3 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 231 of the ALK protein (p.Thr231Arg). This variant is present in population databases (rs142120301, gnomAD 0.03%). 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: 538218). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Sema4, Sema4 RCV002256446 SCV002528535 likely benign Hereditary cancer-predisposing syndrome 2021-10-19 criteria provided, single submitter curation
Ambry Genetics RCV002256446 SCV002668220 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-12 criteria provided, single submitter clinical testing The p.T231R variant (also known as c.692C>G), located in coding exon 2 of the ALK gene, results from a C to G substitution at nucleotide position 692. The threonine at codon 231 is replaced by arginine, an amino acid with 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.
GeneDx RCV003317320 SCV004021902 uncertain significance not provided 2023-01-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25054154)

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