Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000603810 | SCV000731644 | pathogenic | Rare genetic deafness | 2018-08-09 | criteria provided, single submitter | clinical testing | The p.Arg81Gln variant in LRTOMT has been reported in 16 North African (Tunisian and Moroccan) probands with hearing loss, and segregated with hearing loss in > 20 family members, all of whom were homozygous for the variant (Ahmed 2008, Char if 2008). The variant was detected in 5/430 (1.2%) ethnically matched control ch romosomes, however its frequency in the probands (13.8%, 32/232 chromosomes) is significantly higher, which supports a causative role for the variant, and sugge sts that the variant may represent a founder mutation in these populations. In a ddition, computational prediction tools and conservation analyses suggest that t his variant may impact the protein. The variant has also been identified in 3/57 674 European chromosomes by the genome Aggregation Database (gnomAD, http://gnom ad.broadinstitute.org/). In summary, this variant meets criteria to be classifie d as pathogenic for hearing loss in an autosomal recessive manner based upon seg regation studies and enrichment in cases. ACMG/AMP criteria applied: PS4, PP1_St rong, PP3. |
| 3billion, |
RCV000000573 | SCV002059017 | pathogenic | Autosomal recessive nonsyndromic hearing loss 63 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant was co-segregated with Deafness, autosomal recessive 63 in multiple affected family members with additional meioses meeting strong evidence levels (PMID: 18953341, PP1_S). It has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 18953341,PM3_P). A different missense change at the same codon has been reported to be associated with LRTOMT related disorder (PMID:22903915, PM5_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.701, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000026, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| MGZ Medical Genetics Center | RCV000000573 | SCV002581628 | pathogenic | Autosomal recessive nonsyndromic hearing loss 63 | 2022-07-29 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000000573 | SCV000020722 | pathogenic | Autosomal recessive nonsyndromic hearing loss 63 | 2008-11-01 | no assertion criteria provided | literature only |