ClinVar Miner

Submissions for variant NM_001100.3(ACTA1):c.109G>T (p.Val37Leu) (rs1553255521)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558312 SCV000638355 pathogenic Nemaline myopathy 3 2017-06-07 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 37 of the ACTA1 protein (p.Val37Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with nemaline myopathy (PMID: 19562689, 23394784). A different nucleotide change (c.109G>C) that produces the same amino acid change as this variant (p.Val37Leu) has been reported in multiple individuals affected with nemaline myopathy (PMID: 19562689, 12921789, 15236405). In 2 of these cases this variant was reported to arise de novo (PMID: 19562689, 12921789, 15236405). The c.109G>C sequence change has also been reported as p.Val35Leu. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been reported in multiple affected individuals. For these reasons, it has been classified as Pathogenic.
Baylor Genetics RCV000558312 SCV000807332 pathogenic Nemaline myopathy 3 2017-09-01 criteria provided, single submitter clinical testing This mutation has been previously described as disease-causing in the literature, as has another mutation causing the same amino acid substitution. It has been identified once in our laboratory as a de novo mutation in a 1-month-old female with nemaline myopathy, hypotonia, respiratory distress, and cardiac arrest

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