ClinVar Miner

Submissions for variant NM_001614.5(ACTG1):c.721G>A (p.Glu241Lys)

dbSNP: rs267606631
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000211710 SCV000205640 likely pathogenic Rare genetic deafness 2016-09-11 criteria provided, single submitter clinical testing The p.Glu241Lys variant in ACTG1 has been reported in 3 individuals with hearing loss, segregated in 5 relatives with hearing loss from 2 families (Morin 2009, Miyagawa 2015, LMM unpublished data), and was absent from large population studi es. Functional studies performed in yeast suggested that the variant may impact the hair cell's cytoskeletal structure (Morin 2009). Computational prediction to ols and conservation analyses suggest that this variant may impact the protein. In summary, although additional studies are required to fully establish its clin ical significance, this variant is likely pathogenic for autosomal dominant hear ing loss.
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine RCV000019987 SCV000929847 likely pathogenic Autosomal dominant nonsyndromic hearing loss 20 criteria provided, single submitter research
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375049 SCV001571715 likely pathogenic Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PS1_Strong, PM2_Moderate, PP3_Supporting
GeneDx RCV000059728 SCV001786159 likely pathogenic not provided 2021-05-26 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect as yeast expressing E241K demonstrated impaired growth. E241K also influenced cell morphology and actin cytoskeletal patterns, leading to larger cell size and abnormal randomly distributed thick actin cables and patches as well as an aberrant multi-vacuolar pattern (Morin et al., 2009); Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 27627659, 19477959, 25792668, 32341388)
OMIM RCV000019987 SCV000040285 pathogenic Autosomal dominant nonsyndromic hearing loss 20 2009-08-15 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059728 SCV000091298 not provided not provided no assertion provided not provided

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