ClinVar Miner

Submissions for variant NM_002180.2(IGHMBP2):c.1738G>A (p.Val580Ile) (rs137852667)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneReviews RCV000192262 SCV000239910 pathogenic Charcot-Marie-Tooth disease 2015-04-30 no assertion criteria provided literature only
Institute of Human Genetics,Cologne University RCV000664209 SCV000787768 pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1 2018-04-25 no assertion criteria provided clinical testing
Invitae RCV000535929 SCV000642320 likely pathogenic Spinal muscular atrophy, distal, autosomal recessive, 1; Charcot-Marie-Tooth disease, axonal, type 2S 2017-11-13 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 580 of the IGHMBP2 protein (p.Val580Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs137852667, ExAC 0.03%). This variant has been reported in the compound heterozygous or homozygous state in families and individuals affected with spinal muscular atrophy with respiratory distress type 1 (PMID: 11528396, 16765827) and Charcot-Marie-Tooth disease type 2 (PMID: 25439726, 26392352). ClinVar contains an entry for this variant (Variation ID: 9114). Experimental studies have shown that this missense change impairs enzymatic activity in vitro (PMID: 22157136). In summary, this variant is a rare missense change that has been reported in affected individuals and shown to affect protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000009684 SCV000029902 pathogenic Werdnig-Hoffmann disease 2001-09-01 no assertion criteria provided literature only

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