ClinVar Miner

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

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Total submissions: 3
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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.
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

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