Submissions for variant NM_000260.4(MYO7A):c.397dup (p.His133fs)

dbSNP: rs111033187

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000036133	SCV000487442	likely pathogenic	Usher syndrome type 1	2016-11-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000409086	SCV000487443	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 2	2016-11-03	criteria provided, single submitter	clinical testing
Invitae	RCV001212883	SCV001384485	pathogenic	not provided	2023-11-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His133Profs*7) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 21569298, 22898263). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.390_391insC. ClinVar contains an entry for this variant (Variation ID: 43229). For these reasons, this variant has been classified as Pathogenic.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324501	SCV004030425	pathogenic	Usher syndrome	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
PreventionGenetics, part of Exact Sciences	RCV004534756	SCV004117573	pathogenic	MYO7A-related disorder	2023-08-28	criteria provided, single submitter	clinical testing	The MYO7A c.397dupC variant is predicted to result in a frameshift and premature protein termination (p.His133Profs*7). This variant was reported in individuals with Usher syndrome (Bonnet et al. 2011. PubMed ID: 21569298; Bahena et al. 2021. PubMed ID: 34148116). This variant is reported in 0.020% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-76867057-G-GC). Frameshift variants in MYO7A are expected to be pathogenic. This variant is interpreted as pathogenic.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000844713	SCV000059785	likely pathogenic	Rare genetic deafness	2008-03-01	no assertion criteria provided	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291464	SCV001479968	likely pathogenic	Hearing loss, autosomal recessive		no assertion criteria provided	research