Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089576 | SCV001244810 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 77 | 2018-07-01 | criteria provided, single submitter | clinical testing | A heterozygous frameshift deletion variant, NM_144612.6(LOXHD1):c.5885delC, has been identified in exon 38 of 40 of the LOXHD1 gene. This deletion is predicted to create a frameshift starting at amino acid position 1962, introducing a stop codon 137 residues downstream, NP_653213.6(LOXHD1):p.(Thr1962Argfs*137). This variant is predicted to result in loss of protein function either through truncation (including the PLAT domain) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has not been previously reported in clinical cases. Additionally, several truncating variants upstream and downstream of this variant has been reported (ClinVar). Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. |