ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.4488G>C (p.Gln1496His)

dbSNP: rs121908347
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001566890 SCV001790477 pathogenic not provided 2019-08-06 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect by a cryptic intronic splice site 103bp downstream, which indicates a truncation and loss of function of CDH23 (Bolz et al., 2001); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31706454, 31231422, 12075507, 11138009, 18273900, 18429043, 27599893, 29986705)
Labcorp Genetics (formerly Invitae), Labcorp RCV001566890 SCV002247154 pathogenic not provided 2023-02-28 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 1496 of the CDH23 protein (p.Gln1496His). This variant also falls at the last nucleotide of exon 36, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Usher syndrome (PMID: 11138009, 30459346, 31231422). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4915). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 11138009). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003472971 SCV004210642 pathogenic Pituitary adenoma 5, multiple types 2024-03-27 criteria provided, single submitter clinical testing
OMIM RCV000005197 SCV000025374 pathogenic Usher syndrome type 1D 2001-01-01 no assertion criteria provided literature only
Natera, Inc. RCV001835621 SCV002087434 pathogenic Usher syndrome type 1 2020-01-24 no assertion criteria provided clinical testing

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