ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.4273A>G (p.Lys1425Glu) (rs534886444)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000143817 SCV000780944 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing
Mendelics RCV000988269 SCV001137924 benign Amyotrophic lateral sclerosis type 4 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001049421 SCV001213470 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2019-03-07 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 1425 of the SETX protein (p.Lys1425Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs534886444, ExAC 0.009%). This variant has been observed in a family affected with Charcot-Marie-Tooth disease (PMID: 25802885). ClinVar contains an entry for this variant (Variation ID: 155746). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Northcott Neuroscience Laboratory, ANZAC Research Institute RCV000143817 SCV000188710 probable-non-pathogenic not provided no assertion criteria provided not provided Converted during submission to Likely benign.
Inherited Neuropathy Consortium RCV000790205 SCV000929597 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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