ClinVar Miner

Submissions for variant NM_138361.5(LRSAM1):c.2080T>C (p.Cys694Arg) (rs759312530)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468628 SCV000547851 likely pathogenic Charcot-Marie-Tooth disease type 2P 2018-05-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 694 of the LRSAM1 protein (p.Cys694Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs759312530, ExAC 0.002%). This variant has been reported to segregate with autosomal dominant Charcot-Marie-Tooth (CMT) disease in a family (PMID:27615052) and has been reported in several individuals affected with CMT disease (PMID: 27164712, Invitae). ClinVar contains an entry for this variant (Variation ID: 408267). Experimental studies have shown that this missense change altered interactions with RNA-binding proteins and resulted in axonal degeneration in neuronal cell lines (PMID: 27615052). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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