ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1693G>A (p.Asp565Asn) (rs770111639)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705582 SCV000834584 uncertain significance Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 565 of the IGHMBP2 protein (p.Asp565Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs770111639, ExAC 0.005%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 15108294). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been reported in combination with another IGHMBP2 variant in an individual affected with distal hereditary motor neuropathy, type VI (PMID: 22157136, 14681881). Experimental studies have shown that this missense change results in abolished helicase activity of the encoded IGHMBP2 protein (PMID: 19158098, 22157136). 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.
Biochemistry Laboratory of CDMU,Chengde Medical University RCV000768429 SCV000899184 likely pathogenic Charcot-Marie-Tooth disease, axonal, type 2S no assertion criteria provided case-control
Inherited Neuropathy Consortium RCV000790283 SCV000929687 uncertain significance Distal spinal muscular atrophy no assertion criteria provided literature only

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