Submissions for variant NM_005379.4(MYO1A):c.277C>T (p.Arg93Ter)

dbSNP: rs121909305

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151452	SCV000199483	uncertain significance	not specified	2013-11-19	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Arg93X variant in MYO1A has been reported in 1 Italian individual with moderately-severe sensor ineural hearing loss; however it was also present in this individual?s mother wh o reported normal hearing (Donaudy 2003). It has also been identified in 0.5% (4 5/8600) of European American chromosomes and 0.07% (3/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/), as well as in 0.8% (1/120) of Colombian chromosomes by the 1000 Genomes P roject (dbSNP rs121909305). This nonsense variant leads to a premature terminati on codon at position 93, which is predicted to lead to a truncated or absent pro tein. However, it is unclear whether loss of function variants in MYO1A are caus ative for hearing loss. In summary, although we cannot rule out that this varian t may be causative for dominant hearing loss with low penetrance and/or variable expressivity, based upon its high frequency in the general population and its p resence in an unaffected family member of an individual with hearing loss, we wo uld lean towards a more likely benign role.
Eurofins Ntd Llc (ga)	RCV000151452	SCV000336819	likely benign	not specified	2016-04-12	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756406	SCV000884209	benign	not provided	2023-09-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000756406	SCV001845876	benign	not provided	2018-07-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29308629, 27759032, 25262649, 24616153, 26086970, 12736868, 25525159)
CeGaT Center for Human Genetics Tuebingen	RCV000756406	SCV004133504	likely benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	MYO1A: BS1
OMIM	RCV000008623	SCV000028831	uncertain significance	Autosomal dominant nonsyndromic hearing loss 48	2014-05-01	no assertion criteria provided	literature only
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000008623	SCV000268684	likely benign	Autosomal dominant nonsyndromic hearing loss 48	2016-05-10	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000756406	SCV001743341	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000756406	SCV001917591	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756406	SCV001974741	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003904823	SCV004719540	likely benign	MYO1A-related disorder	2020-02-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).