ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1273C>T (p.Arg425Cys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806743 SCV000946758 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 425 of the IGHMBP2 protein (p.Arg425Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with spinal muscular atrophy with respiratory distress (PMID: 22791546). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000853264 SCV000996092 likely pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1 2017-12-19 criteria provided, single submitter clinical testing This variant was previously reported in a compound heterozygous state in an infant with infantile spinal muscular atrophy with respiratory distress type 1 (PMID: 22791546). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0012% (3/246146). This variant has not been functionally characterized to our knowledge. However, multiple in silico analysis predict the variant to be damaging. Based on the combined evidence, the p.Gly260Arg variant is classified as likely pathogenic.
Inherited Neuropathy Consortium RCV000789974 SCV000929363 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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