ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.734A>G (p.Asn245Ser) (rs1555243999)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Inherited Neuropathy Consortium RCV000789971 SCV000929359 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000642625 SCV000764312 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-04-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 245 of the IGHMBP2 protein (p.Asn245Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the heterozygous state in individuals affected with Charcot-Marie-Tooth (CMT) disease type 2 and gait difficulty (PMID: 25439726, 26922252). This variant has been reported in combination with other IGHMBP2 variants in an individual affected with CMT disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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