Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Variantyx, |
RCV000036073 | SCV007593683 | pathogenic | Usher syndrome type 1 | 2025-04-09 | criteria provided, single submitter | clinical testing | This is a nonsense variant in the MYO7A gene (OMIM: 276903). Pathogenic variants in this gene have been associated with autosomal recessive Usher syndrome type IB. This variant introduces a premature termination codon in exon 17 out of 49 and is expected to result in loss of function, which is a known disease mechanism for MYO7A in this disorder (PMID: 8900236, 25404053) (PVS1). This variant has been reported in the homozygous or compound heterozygous state in at least 3 unrelated affected individuals (PMID: 21436283, 21569298, 25333064) (PM3). It has a 0.0087% maximum allele frequency in non-founder control populations (https://gnomad.broadinstitute.org/) (PM2). Based on the current evidence, this variant is classified as pathogenic for autosomal recessive Usher syndrome type IB. |
| Prevention |
RCV004528175 | SCV004112839 | pathogenic | MYO7A-related disorder | 2023-05-01 | criteria provided, single submitter | clinical testing | The MYO7A c.2005C>T variant is predicted to result in premature protein termination (p.Arg669*). This variant has been reported in compound heterozygous and homozygous state in multiple individuals with Usher syndrome type 1B (see for example - Roux et al. 2011. PubMed ID: 21436283; Table S1 - Bonnet et al. 2016. PubMed ID: 27460420; Table S2 - Carss et al. 2017. PubMed ID: 28041643; Table S1 - Khateb et al. 2019. PubMed ID: 31479088). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-76885871-C-T). Nonsense variants in MYO7A are expected to be pathogenic. This variant is interpreted as pathogenic. |
| Natera, |
RCV001272498 | SCV001454570 | pathogenic | Usher syndrome type 1B | 2025-11-17 | criteria provided, single submitter | clinical testing | The c.2005C>T variant in MYO7A is a nonsense variant predicted to introduce a stop codon at amino acid 669. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 21436283, 27460420). Given the available evidence, this variant is classified as Pathogenic. |
| Ce |
RCV000443077 | SCV001247934 | pathogenic | not provided | 2019-08-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000443077 | SCV001220993 | pathogenic | not provided | 2025-12-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg669*) 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 (rs111033201, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with autosomal recessive Usher syndrome or non-syndromic deafness (PMID: 21436283, 21569298, 25333064, 25788563, 27460420, 28041643). ClinVar contains an entry for this variant (Variation ID: 43169). For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV000763277 | SCV000893921 | pathogenic | Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000443077 | SCV000862221 | pathogenic | not provided | 2018-06-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000443077 | SCV000521011 | pathogenic | not provided | 2020-12-02 | criteria provided, single submitter | clinical testing | 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: 32581362, 31266775, 31479088, 29892088, 27460420, 25333064, 25468891, 21436283, 21569298, 21873662, 9718356, 25525159) |
| Laboratory for Molecular Medicine, |
RCV000844716 | SCV000059725 | pathogenic | Rare genetic deafness | 2013-11-22 | criteria provided, single submitter | clinical testing | The p.Arg669X variant in MYO7A has been previously reported in at least 4 indivi duals with Usher syndrome (Bonnet 2011, Roux 2011, LMM-unpublished data). It has also been identified in 0.003% (5/127112) of European chromosomes by gnomAD (ht tp://gnomad.broadinstitute.org), though this frequency in the general population is consistent with a recessive carrier frequency. This nonsense variant leads t o a premature termination codon at position 669, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be clas sified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP criteria a pplied: PVS1, PM2, PM3. |
| NIHR Bioresource Rare Diseases, |
RCV000504864 | SCV000599116 | pathogenic | Usher syndrome | 2015-01-01 | no assertion criteria provided | research | |
| Counsyl | RCV000409801 | SCV000487455 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 2 | 2016-11-02 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |
| Counsyl | RCV000036073 | SCV000487454 | likely pathogenic | Usher syndrome type 1 | 2016-11-02 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |