Submissions for variant NM_001614.5(ACTG1):c.760C>T (p.Arg254Trp)

dbSNP: rs281875328

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000059729	SCV001819928	likely pathogenic	not provided	2022-07-07	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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 (HGMD); This variant is associated with the following publications: (PMID: 22366783, 28496999, 27240540)
Institute of Human Genetics, University of Leipzig Medical Center	RCV000022426	SCV001976431	likely pathogenic	Baraitser-winter syndrome 2	2021-10-04	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed).
Genetic Services Laboratory, University of Chicago	RCV000059729	SCV002072040	likely pathogenic	not provided	2017-08-09	criteria provided, single submitter	clinical testing
Invitae	RCV001851994	SCV002174610	pathogenic	Autosomal dominant nonsyndromic hearing loss 20; Baraitser-winter syndrome 2	2022-02-05	criteria provided, single submitter	clinical testing	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: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 29589). This missense change has been observed in individual(s) with Baraitser-Winter syndrome (PMID: 22366783, 27240540). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 254 of the ACTG1 protein (p.Arg254Trp). For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV003137540	SCV003807306	likely pathogenic	Autosomal dominant nonsyndromic hearing loss 20	2022-11-12	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4 moderated, PM2 moderated, PM6 moderated, PP2 supporting, PP3 supporting
OMIM	RCV000022426	SCV000043715	pathogenic	Baraitser-winter syndrome 2	2012-02-26	no assertion criteria provided	literature only
UniProtKB/Swiss-Prot	RCV000059729	SCV000091299	not provided	not provided		no assertion provided	not provided
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291054	SCV001479416	likely pathogenic	Lissencephaly		no assertion criteria provided	research