ClinVar Miner

Submissions for variant NM_016188.5(ACTL6B):c.1027G>A (p.Gly343Arg) (rs1131692228)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000785974 SCV000583961 pathogenic Intellectual developmental disorder with severe speech and ambulation defects 2019-06-27 criteria provided, single submitter research
SIB Swiss Institute of Bioinformatics RCV000785974 SCV000996404 likely pathogenic Intellectual developmental disorder with severe speech and ambulation defects 2019-07-28 criteria provided, single submitter curation This variant is interpreted as a Likely pathogenic for Intellectual developmental disorder with severe speech and ambulation defects, autosomal dominant. The following ACMG Tag(s) were applied: PM2, PS4-Moderate, PM6, PP3.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000785974 SCV001367730 uncertain significance Intellectual developmental disorder with severe speech and ambulation defects 2018-11-30 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PP5.
Institute of Human Genetics, University of Leipzig Medical Center RCV000785974 SCV001429548 uncertain significance Intellectual developmental disorder with severe speech and ambulation defects 2016-08-05 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed).
Invitae RCV001381390 SCV001579767 pathogenic not provided 2020-07-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 343 of the ACTL6B protein (p.Gly343Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with a neurodevelopmental disorder with severe speech and ambulation defects (PMID: 31031012). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 430804). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526602 SCV001737031 pathogenic Intellectual disability criteria provided, single submitter clinical testing
Baylor Genetics RCV001533053 SCV001748873 pathogenic ACTL6B-related BAFopathy 2021-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001381390 SCV001767095 pathogenic not provided 2021-06-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31036916, 27535533, 32873422, 26582918, 32312822, 28191890, 31031012, 28628100, 28867141, 28135719)
OMIM RCV000785974 SCV000924559 pathogenic Intellectual developmental disorder with severe speech and ambulation defects 2019-06-19 no assertion criteria provided literature only
CHU Sainte-Justine Research Center,University of Montreal RCV001028074 SCV001190857 likely pathogenic Autistic disorder of childhood onset; ACTL6B-related dominant intellectual disability 2019-03-01 no assertion criteria provided research

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