Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000223213 | SCV000271414 | pathogenic | Rare genetic deafness | 2016-06-30 | criteria provided, single submitter | clinical testing | The p.Glu396fs variant in MYO15A has been previously reported in two individuals with hearing loss including one homozygote state and segregated with disease in 2 affected siblings (Bashir 2012, LMM data). This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at posit ion 396 and leads to a premature termination codon 36 amino acids downstream. Th is alteration is then predicted to lead to a truncated or absent protein. In sum mary, this variant meets our criteria to be classified as pathogenic for hearing loss in an autosomal recessive manner based on the predicted impact of the vari ant and segregation evidence. |
Victorian Clinical Genetics Services, |
RCV000851286 | SCV001244798 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2018-07-31 | criteria provided, single submitter | clinical testing | A heterozygous frameshift duplication variant, NM_016239.3(MYO15A):c.1185dupC, has been identified in exon 2 of 66 of the MYO15A gene. This duplication is predicted to create a frameshift starting at amino acid position 396, introducing a stop codon 36 residues downstream (NP_057323.3(MYO15A):p.(Glu396Argfs*36)). This variant is predicted to result in loss of protein function either through truncation (including the loss of multiple domains) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is present in the gnomAD database at a frequency of 0.0047% (13 heterozygotes and 0 homozygotes). It has been previously described as pathogenic and segregated with disease in two families (Bashir R. et al. (2012), Miyagawa M. et al. (2015)). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC. |
Molecular Diagnosis Center for Deafness | RCV000851286 | SCV001984879 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV001853427 | SCV002215332 | pathogenic | not provided | 2024-01-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu396Argfs*36) 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 (rs746288259, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with nonsyndromic deafness (PMID: 22245518, 31827275). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 228372). For these reasons, this variant has been classified as Pathogenic. |
3billion | RCV000851286 | SCV002521764 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2022-05-22 | 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: 0.006%). Frameshift: 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 without evidence for the classification (ClinVar ID: VCV000228372 / PMID: 22245518 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Gene |
RCV001853427 | SCV005324914 | pathogenic | not provided | 2023-08-23 | criteria provided, single submitter | clinical testing | 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: 31589614, 37734845, 31827275, 33784549, 22245518, 35346193, 35248088) |
Laboratory of Molecular Genetics, |
RCV000851286 | SCV000986689 | pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2019-08-28 | no assertion criteria provided | research | The individual with congenital NSHL carried single frameshift variant in MYO15A as well as single missense variant in the different locus in the same gene. They were segregated with the disease in his family and patient was a sporadic case in it. NSHL carried by the patient was categorized as a type of severe and profound hearing loss based on audiogram. |