Submissions for variant NM_001614.5(ACTG1):c.1003C>T (p.Arg335Cys)

dbSNP: rs1568060200

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000680688	SCV000808132	pathogenic	not provided	2024-11-06	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 38592426, 36205783)
Baylor Genetics	RCV001334940	SCV001527953	likely pathogenic	Autosomal dominant nonsyndromic hearing loss 20	2018-03-21	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. A similar variant affecting the same amino acid, c.1004G>A (p.R335H), has been previously reported as de novo in one patient with Baraitser-Winter cerebrofrontofacial syndrome [PMID: 27240540]
CeGaT Center for Human Genetics Tuebingen	RCV000680688	SCV001747184	likely pathogenic	not provided	2021-05-01	criteria provided, single submitter	clinical testing
3billion	RCV001334940	SCV002572539	pathogenic	Autosomal dominant nonsyndromic hearing loss 20	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change (ClinVar ID: VCV000561396) and a different missense change at the same codon (p.Arg335His/ ClinVar ID: VCV000520655 ) have been previously reported as pathogenic/likely pathogenic with strong evidence. Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity	RCV000680688	SCV003822548	uncertain significance	not provided	2020-11-24	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000680688	SCV001952617	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000680688	SCV001974313	likely pathogenic	not provided		no assertion criteria provided	clinical testing