Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001002598 | SCV000361955 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| ARUP Laboratories, |
RCV001002598 | SCV001160571 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2019-05-23 | criteria provided, single submitter | clinical testing | The MYO3A c.3398+3A>G variant (rs373758358), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 299670). This variant is found in the non-Finnish European population with an allele frequency of 0.030% (38/125952 alleles) in the Genome Aggregation Database. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by significantly weakening the nearby canonical donor splice site. However, without RNA studies the effect on splicing is unknown. Thus, given the lack of clinical and functional data, the significance of the c.3398+3A>G variant is uncertain at this time. |
| Gene |
RCV001546540 | SCV001766072 | uncertain significance | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on splicing |
| Invitae | RCV001546540 | SCV002122836 | uncertain significance | not provided | 2023-03-28 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 299670). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs373758358, gnomAD 0.03%). This sequence change falls in intron 29 of the MYO3A gene. It does not directly change the encoded amino acid sequence of the MYO3A protein. It affects a nucleotide within the consensus splice site. |
| Revvity Omics, |
RCV001002598 | SCV003817825 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 30 | 2019-09-12 | criteria provided, single submitter | clinical testing |