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
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
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

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