Submissions for variant NM_138361.5(LRSAM1):c.1913-1G>A (rs756880678)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000693004	SCV000820857	pathogenic	Charcot-Marie-Tooth disease type 2P	2018-03-06	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 23 of the LRSAM1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs756880678, ExAC 0.002%). This variant has been reported to segregate in a autosomal recessive fashion with Charcot-Marie-Tooth disease type 2 in a family (PMID: 20865121). ClinVar contains an entry for this variant (Variation ID: 204301). Experimental studies have shown that this splice acceptor change results in aberrant splicing of the LRSAM1 gene, resulting in a frameshift and absence of protein in cultured patient cells  (PMID: 20865121). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LRSAM1 are known to be pathogenic (PMID: 20865121). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV000192257	SCV001336729	pathogenic	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
GeneReviews	RCV000192257	SCV000239905	pathogenic	Charcot-Marie-Tooth disease	2015-04-30	no assertion criteria provided	literature only
Inherited Neuropathy Consortium	RCV000192257	SCV000928713	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only