Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000213556 | SCV000272093 | uncertain significance | not specified | 2018-04-11 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Arg1208Cys va riant in MYO15A has been previously identified by our laboratory in two individu als with hearing loss; however, a variant in trans was not identied in either of these individuals. This variant has been identified in 0.2% (60/30752) of South Asian chromosomes and 0.1% (132/126234) of European chromosomes by the Genome A ggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201618718 ). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analysis do not provide strong support for or against an impac t to the protein; however, arginine at position 1208 is not conserved and severa l evolutionarily distant species carry a cysteine, raising the possibility that this change may be tolerated. In summary, while the clinical significance of the p.Arg1208Cys variant is uncertain, its lack of conservation suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BP4 |
Illumina Laboratory Services, |
RCV001126421 | SCV001285616 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 3 | 2018-01-12 | 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. |
Baylor Genetics | RCV001126421 | SCV001526616 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 3 | 2018-02-08 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV001589134 | SCV001814527 | uncertain significance | not provided | 2023-07-24 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Al Jalila Children's Genomics Center, |
RCV001126421 | SCV001984462 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 3 | 2020-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001589134 | SCV002404148 | benign | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001589134 | SCV004224324 | uncertain significance | not provided | 2022-08-30 | criteria provided, single submitter | clinical testing | BS1_supporting |