Submissions for variant NM_017433.5(MYO3A):c.3499del (p.Ser1167fs)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 3

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757542	SCV000885805	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 30	2018-08-29	criteria provided, single submitter	clinical testing	The p.Ser1167fs variant (rs752046945) has not been reported in the medical literature, but it is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.053% in the East Asian population (identified in 10 out of 18,858 chromosomes), which is consistent with a recessive carrier frequency. Deletion of the thymine at nucleotide 3499 causes a frameshift in the MYO3A gene at codon 1167, which creates a premature stop codon that is predicted to result in a truncated or absent protein product. Other truncating variants in MYO3A have been reported in individuals with non-syndromic hearing loss (Sommen 2016 and Walsh 2002). Therefore, based on the available evidence, the p.Ser1167fs variant is classified as likely pathogenic.
GeneDx	RCV002221580	SCV002499034	uncertain significance	not provided	2022-03-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV002221580	SCV004615995	pathogenic	not provided	2023-06-25	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: 618746). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs752046945, gnomAD 0.05%). This sequence change creates a premature translational stop signal (p.Ser1167Profs*26) in the MYO3A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO3A are known to be pathogenic (PMID: 12032315, 23990876).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.