ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1817G>A (p.Arg606His) (rs1240319744)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001376977 SCV001574190 likely pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 606 of the IGHMBP2 protein (p.Arg606His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with IGHMBP2-related conditions (PMID: 24022109). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 637480). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IGHMBP2 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Inherited Neuropathy Consortium RCV000789679 SCV000929054 uncertain significance Autosomal dominant distal hereditary motor neuropathy no assertion criteria provided literature only

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