Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000756726 | SCV000884618 | likely pathogenic | not provided | 2017-06-07 | criteria provided, single submitter | clinical testing | The p.Arg1338Ter variant (rs755471554) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. The c.4012C>T variant creates a termination codon in the STRC protein at codon 1338 in exon 20 out of 29 which is predicted to result in a truncated or absent protein product. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.01 percent (identified on 5 out of 34,394 chromosomes). Based on these observations, the p.Arg1338Ter has been classified as likely pathogenic. |
| King Laboratory, |
RCV003155303 | SCV003844149 | pathogenic | Autosomal recessive nonsyndromic hearing loss 16 | 2023-02-28 | criteria provided, single submitter | research | This variant occurred in compound heterozygosity with an STRC full gene deletion in a patient with bilateral sensorineural hearing loss of onset <18 years, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient has a paternal 1st cousin with syndromic hearing loss of childhood onset, and the family has no other history of hearing loss. This variant is a nonsense leading to an early stop at position 1338 of 1775 in the stereocilin protein. As of January 2023, this variant has been reported to ClinVar as likely pathogenic and is found in 9 heterozygotes on gnomAD. Based on the prediction that this variant leads to a truncated protein, compound heterozygosity with a loss-of-function variant, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic. |