ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.553C>T (p.Arg185Cys) (rs1064794287)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541948 SCV000638368 pathogenic Nemaline myopathy 3 2017-06-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 185 of the ACTA1 protein (p.Arg185Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in families and individuals affected with severe nemaline myopathy (PMID: 10508519, 24313005, 15226407). This variant is also known as p.Arg183Cys in the literature. Experimental studies have shown that this missense change does not impair polymerization in vitro (PMID: 15226407). A different missense substitution at this codon (p.Arg185Gly, also referred to as p.Arg183Gly) has been determined to be pathogenic (PMID: 12921789, 15198992, 11333380, 25470062, 15226407). This suggests that the arginine residue is critical for ACTA1 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.

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