ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.782A>T (p.Glu261Val) (rs121909523)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000019945 SCV000834826 likely pathogenic Nemaline myopathy 3 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with valine at codon 261 of the ACTA1 protein (p.Glu261Val). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with other ACTA1 variants in individuals affected with autosomal recessive nemaline myopathy (PMID: 10508519, 15236405). This variant is also known as p.Glu259Val in the literature. ClinVar contains an entry for this variant (Variation ID: 18283). Experimental studies have shown that this missense change results in protein misfolding (PMID: 15226407). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, 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.
OMIM RCV000019945 SCV000040243 pathogenic Nemaline myopathy 3 1999-10-01 no assertion criteria provided literature only

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