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 pathogenic Charcot-Marie-Tooth disease type 2P 2019-08-29 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). This variant disrupts the p.Cys694 amino acid residue in LRSAM1. Other variant(s) that disrupt this residue have been observed in individuals with LRSAM1-related conditions (PMID: 27686364), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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