Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000612673 | SCV000731445 | uncertain significance | not specified | 2017-01-24 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Glu2588His va riant in CDH23 results from the benign c.7762G>C variant and the c.7764G>T varia nt of uncertain significance. These two single nucleotide variants were determi ned to be in cis using NGS read data, and they affect the same codon, resulting in a glutamic acid to a histidine alteration at position 2588. The c.7762G>C va riant is present in 2.9% (283/9860) of South Asian chromosomes by the Exome Aggr egation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs41281338); how ever, the c.7764G>T variant has not been identified in large population studies. The glutamic acid at position 2588 is not conserved through mammals or evolutio nary distant species, with >10 bird species having a histidine at this position. In summary, while the clinical significance of the p.Glu2588His variant is unc ertain, the conservation data suggest that it is more likely to be benign. |