ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.812T>G (p.Met271Arg) (rs1553255360)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557960 SCV000638381 likely pathogenic Nemaline myopathy 3 2017-06-19 criteria provided, single submitter clinical testing This sequence change replaces methionine with arginine at codon 271 of the ACTA1 protein (p.Met271Arg). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in 3 individuals affected with nemaline myopathy and shown to arise de novo in 2 affected individuals (PMID: 11166164, 19562689, Invitae database). This variant is also known as M269R in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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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