ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1344-2A>G

dbSNP: rs111033415
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036047 SCV000059699 pathogenic Rare genetic deafness 2017-09-12 criteria provided, single submitter clinical testing The c.1344-2A>G variant in MYO7A has been reported in four individuals with Ushe r syndrome (Maubaret 2005, LMM data). One of them was homozygous for the variant and three other individuals were compound heterozygous with a second pathogenic MYO7A variant. This variant has not been identified in large population studies . In addition, this variant occurs in the invariant region (+/- 1/2) of the spli ce consensus sequence and is predicted to cause altered splicing leading to an a bnormal or absent protein. In summary, this variant meets criteria to be classif ied as pathogenic for Usher syndrome in an autosomal recessive manner.
Counsyl RCV000665311 SCV000789408 pathogenic Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-02-08 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814023 SCV001755202 pathogenic Ear malformation 2021-07-10 criteria provided, single submitter clinical testing
INGEBI, INGEBI / CONICET RCV001544528 SCV001763574 pathogenic Nonsyndromic genetic hearing loss 2021-07-15 criteria provided, single submitter clinical testing Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria:The c.1344-2 A>G variant in MYO7A gene is absent from population databases meeting PM2. This type of variant is predicted to generate a lost of the aceptor splicing site in MYO7A gene affecting gene MYO7A, which is a known mechanism of disease, PVS1. The c.1344-2 A>G has been identified in trans with a pathogenic variant in an Ushers patient with altered balance (PMID:15823922). Besides, it was identified in homocygous state in two different families (one with severe-profound non-syndrmic hearing loss and the other with Usher Syndromce) and an sporadic case with Usher Syndrome; PMID: 26445815, 27460420.); PP4. In thi work, c.1344-2 A>G was detected in trans with a pathogenic variant in MYO7A gene in a child with non-syndormic hearing loss (ophtalmic features could appear in the youth); PM3_S. Taking into account all the information together: PM2, PVS1, PM3_S, PP4 the variant is classified as Pathogenics for non-syndromic hearing loss and Usher Syndrome.
Labcorp Genetics (formerly Invitae), Labcorp RCV001852738 SCV002236652 pathogenic not provided 2023-11-25 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 12 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 autosomal recessive deafness and/or autosomal recessive Usher syndrome (PMID: 15823922, 26445815, 27460420). This variant is also known as c.1244-2A>G. ClinVar contains an entry for this variant (Variation ID: 43143). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001852738 SCV002526468 pathogenic not provided 2022-06-17 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15823922, 31479088)
Natera, Inc. RCV001831626 SCV002086575 pathogenic Usher syndrome type 1B 2021-02-25 no assertion criteria provided clinical testing

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