Submissions for variant NM_000260.4(MYO7A):c.93C>A (p.Cys31Ter)

dbSNP: rs35689081

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154341	SCV000204004	pathogenic	Rare genetic deafness	2017-08-03	criteria provided, single submitter	clinical testing	The p.Cys31X variant in MYO7A has been reported in at least 9 individuals with U sher syndrome type I, many of whom were either homozygous for this variant or co mpound heterozygous with a second pathogenic variant (Weston 1996, Janecke 1999, Jacobson 2008, Tranebj?rg 2011). It has been identified in 10/123920 European c hromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstit ute.org/; dbSNP rs35689081); this frequency in the general population is consist ent with a carrier frequency for autosomal recessive Usher syndrome. This nonsen se variant leads to a premature stop codon at position 31, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based upon its predicted impact and biallelic presence in previously reported affected ind ividuals.
Counsyl	RCV000665804	SCV000789982	pathogenic	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2017-03-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001226256	SCV001398563	pathogenic	not provided	2024-03-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys31*) 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). This variant is present in population databases (rs35689081, gnomAD 0.008%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 8900236, 10094549, 19074810, 27957503). It is commonly reported in individuals of Danish ancestry (PMID: 27957503). ClinVar contains an entry for this variant (Variation ID: 11859). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001226256	SCV004036907	pathogenic	not provided	2023-09-19	criteria provided, single submitter	clinical testing	Observed in the heterozygous state in an individual with Usher syndrome in published literature (Weston et al., 1996; Janecke et al., 1999; Jacobson et al., 2009); Nonsense 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; This variant is associated with the following publications: (PMID: 27957503, 25525159, 10094549, 20544672, 12112664, 28731162, 24199935, 8900236, 19074810, 25333064, 23770805, 30303587, 31266775, 34948090, 30718709)
OMIM	RCV000012634	SCV000032869	pathogenic	Usher syndrome type 1B	1999-01-01	no assertion criteria provided	literature only
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787856	SCV000926871	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Natera, Inc.	RCV000012634	SCV001461533	pathogenic	Usher syndrome type 1B	2020-09-16	no assertion criteria provided	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291462	SCV001479966	likely pathogenic	Hearing loss, autosomal recessive		no assertion criteria provided	research