ClinVar

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Arg1073Gln va riant in STRC has been previously reported in three individuals with hearing los s (LMM unpublished data), one of whom had a pathogenic variant and the p.Cys1092 Tyr variant of uncertain significance in STRC; however, the cis/trans configurat ion of the variants was not determined. A second STRC variant was not detected i n the other two individuals (LMM unpublished data). This variant has been identi fied in 0.5% (4/888) of European chromosomes and in 0.4% (2/492) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs727503449); however, this allele frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation anal yses suggest that the variant may not impact the protein, though this informatio n is not predictive enough to rule out pathogenicity. In summary, while the clin ical significance of the p.Arg1073Gln variant is uncertain, the population frequ ency data suggests that it is more likely to be benign.