ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.449C>G (p.Thr150Ser) (rs1553255479)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000639666 SCV000761246 pathogenic Nemaline myopathy 3 2017-12-07 criteria provided, single submitter clinical testing This sequence change replaces threonine with serine at codon 150 of the ACTA1 protein (p.Thr150Ser). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with intranuclear rod myopathy and generalized hypotonia (PMID: 19562689, Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). Three different missense substitutions at this codon (p.Thr150Ala, p.Thr150Asn, p.Thr150Ile) have been reported in individuals affected with nemaline myopathy and intranuclear rod myopathy (PMID: 24852243, 12921789, 24787270). These observations suggest that this novel missense substitution at this residue may affect protein function, but this has not been confirmed by published studies. For these reasons, this variant has been classified as Pathogenic.

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