ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1591C>A (p.Pro531Thr) (rs756985703)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000642641 SCV000764328 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 531 of the IGHMBP2 protein (p.Pro531Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs756985703, ExAC 0.05%). This variant has been reported in combination with another IGHMBP2 variant in an individual affected with Charcot-Marie Tooth disease type 2 and Down syndrome (PMID: 25439726). ClinVar contains an entry for this variant (Variation ID: 204302). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Inherited Neuropathy Consortium RCV000192261 SCV000929360 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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