Submissions for variant NM_000260.4(MYO7A):c.2283-1G>T

dbSNP: rs397516295

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000844717	SCV000059734	pathogenic	Rare genetic deafness	2012-03-20	criteria provided, single submitter	clinical testing	The c.2283-1G>T variant in MYO7A has been reported in 8 probands with Usher synd rome (Roux 2011, Bonnet 2011, Jaijo 2011, Roux 2006). 6/8 of these probands were homozygous and 2/8 compound heterozygous. The variant segregated with the disea se in one family and it was absent from 200 control chromosomes (Jaijo 2011). Th e variant alters the invariant region of the 3' splice sequence which leads to s kipping of exon 20, as shown by the analysis of the RNA (Jaijo 2011). In summar y, this variant meets our criteria to be classified as pathogenic for autosomal recessive Usher syndrome.
Counsyl	RCV000666504	SCV000790809	pathogenic	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2018-05-30	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001329739	SCV001521259	pathogenic	Autosomal dominant nonsyndromic hearing loss 11	2019-09-13	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID: 16679490, 25798947, 20497194, 25404053, ClinVar ID: 43178]
Invitae	RCV001383209	SCV001582289	pathogenic	not provided	2023-11-07	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 19 of the MYO7A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Usher syndrome (PMID: 16679490, 20497194, 25404053, 25798947, 31479088). ClinVar contains an entry for this variant (Variation ID: 43178). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20497194). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001383209	SCV001811922	pathogenic	not provided	2020-11-24	criteria provided, single submitter	clinical testing	Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33576163, 31589614, 31479088, 27583663, 27440999, 20301442, 21569298, 21436283, 16679490, 25798947, 25404053, 20497194, 23647439, 24498627, 17361009, 25560255)
3billion	RCV000036082	SCV002059054	pathogenic	Usher syndrome type 1	2022-01-03	criteria provided, single submitter	clinical testing	Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000043178, 3billion dataset). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneReviews	RCV000036082	SCV000268742	not provided	Usher syndrome type 1		no assertion provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001383209	SCV001957663	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001383209	SCV001969914	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831630	SCV002086607	pathogenic	Usher syndrome type 1B	2021-04-02	no assertion criteria provided	clinical testing