Submissions for variant NM_022124.6(CDH23):c.2341G>A (p.Ala781Thr)

gnomAD frequency: 0.00031  dbSNP: rs375918283

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155046	SCV000204730	uncertain significance	not specified	2013-12-05	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Ala781Thr varia nt in CDH23 has not been previously reported in individuals with hearing loss, b ut was identified in 0.04% (2/4214) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; rs37591828). Compu tational analyses (biochemical amino acid properties, conservation, AlignGVGD, P olyPhen2, and SIFT) suggest that the Ala781Thr variant may not impact the protei n, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant cannot be determined with c ertainty; however based upon the arguments described above, we would lean toward s a more likely benign role.
Invitae	RCV001051031	SCV001215164	likely benign	not provided	2024-01-28	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275940	SCV001461620	uncertain significance	Usher syndrome type 1	2020-01-24	no assertion criteria provided	clinical testing