Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Juno Genomics, |
RCV000989770 | SCV007495984 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | clinical testing | Null variant in a gene where loss of function (LOF) is a known mechanism of disease.;For recessive disorders, detected in trans with a pathogenic variant. | |
| Medical and Scientific Branch, |
RCV006449379 | SCV007330055 | pathogenic | Carney complex, type 1 | 2025-12-11 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV000989770 | SCV005645961 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2024-06-07 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001732007 | SCV004298135 | pathogenic | not provided | 2025-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser1176Valfs*14) in the MYO15A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO15A are known to be pathogenic (PMID: 17546645). This variant is present in population databases (rs766187994, gnomAD 0.2%). This premature translational stop signal has been observed in individuals with early onset deafness (PMID: 26810297, 30953472, 31581539, 34416374, 34599368, 34974475, 35346193). It has also been observed to segregate with disease in related individuals. This variant is also known as c.3525_3526insA, p.Q1175fsX1188. ClinVar contains an entry for this variant (Variation ID: 803332). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000989770 | SCV004222854 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2023-11-17 | criteria provided, single submitter | clinical testing | Variant summary: MYO15A c.3524dupA (p.Ser1176ValfsX14) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00014 in 246816 control chromosomes. c.3524dupA has been reported in the literature inmultiple individuals affected with Autosomal Recessive Nonsyndromic Hearing Loss 3 (e.g., Fu_2022). These data indicate that the variant are likely associated with disease. The following publication have been ascertained in the context of this evaluation (PMID: 35939872). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and all submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| 3billion | RCV000989770 | SCV002573120 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.015%). Frameshift variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000803332 / PMID: 26810297). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Molecular Diagnosis Center for Deafness | RCV000989770 | SCV001984891 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | clinical testing | ||
| Gene |
RCV001732007 | SCV001981919 | pathogenic | not provided | 2025-07-11 | criteria provided, single submitter | clinical testing | Identified in a patient with autosomal recessive sensorineural hearing loss who harbored a second MYO15A variant (phase unknown) in published literature (PMID: 30953472); Identified in 9/44 members of a Taiwanese cohort with autosomal recessive sensorineural hearing loss in published literature (PMID: 31581539) but additional evidence is not available; Frameshift 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: 35346193, 31581539, 34325055, 34416374, 34599368, 34943631, 35939872, 26810297, 34974475, 35982127, 38297847, 30953472) |
| Laboratory of Molecular, |
RCV000989770 | SCV001792220 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | research | in compound heterozygosis with the c.1615C>T variant in a subject with bilateral non-syndromic sensorineural prelingual hearing loss (sporadic) | |
| Mendelics | RCV000989770 | SCV001140323 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004746190 | SCV005364326 | pathogenic | MYO15A-related disorder | 2024-04-05 | no assertion criteria provided | clinical testing | The MYO15A c.3524dupA variant is predicted to result in a frameshift and premature protein termination (p.Ser1176Valfs*14). This variant has been reported in the homozygous state and was found to segregate with hearing loss in two families (Li et al. 2016. PubMed ID: 26810297; Liu et al. 2022. PubMed ID: 35939872). It has been reported along with a second pathogenic variant in several individuals with moderate to profound hearing loss (Batissoco et al. 2021. PubMed ID: 34599368; Fu et al. 2022. PubMed ID: 35346193; Guan et al. 2021. PubMed ID: 34416374). This variant is reported in 0.22% of alleles in individuals of East Asian descent in gnomAD. Frameshift variants in MYO15A are expected to be pathogenic. This variant is interpreted as pathogenic. |