ClinVar Miner

Submissions for variant NM_001100.4(ACTA1):c.682G>T (p.Glu228Ter)

dbSNP: rs1558081664
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995477 SCV001149663 pathogenic Congenital myopathy with fiber type disproportion 2017-10-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869389 SCV002110120 pathogenic Actin accumulation myopathy 2022-06-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 807361). This premature translational stop signal has been observed in individual(s) with autosomal recessive ACTA1-related conditions (PMID: 29172004). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu228*) in the ACTA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACTA1 are known to be pathogenic (PMID: 19562689).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587005 SCV005076750 pathogenic Congenital myopathy 2c, severe infantile, autosomal dominant 2024-04-10 criteria provided, single submitter clinical testing Variant summary: ACTA1 c.682G>T (p.Glu228X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for ACTA1-related AR alpha-actinopathy. The variant was absent in 250632 control chromosomes. c.682G>T has been reported in the literature in at-least one individual from a cohort of Early-Onset Myopathies, however detailed information was not available (Vill_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29172004). ClinVar contains an entry for this variant (Variation ID: 807361). Based on the evidence outlined above, the variant was classified as pathogenic.

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