ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.496+1G>A (rs138138689)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411458 SCV000487585 pathogenic Usher syndrome, type 1C 2016-11-02 criteria provided, single submitter clinical testing
Counsyl RCV000412131 SCV000487586 pathogenic Deafness, autosomal recessive 18 2016-11-02 criteria provided, single submitter clinical testing
Invitae RCV001240003 SCV001412918 pathogenic not provided 2020-10-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 5 of the USH1C gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs138138689, ExAC 0.009%). This variant has been observed in several individuals affected with Usher syndrome type I and non-syndromic hearing loss (PMID: 11139240, 27743452, 22135276, 24416283). ClinVar contains an entry for this variant (Variation ID: 371732). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USH1C are known to be pathogenic (PMID: 10973247, 17407589, 20301442, 21203349). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266797 SCV001444976 pathogenic Inborn genetic diseases 2018-05-08 criteria provided, single submitter clinical testing
GeneDx RCV001240003 SCV001785330 pathogenic not provided 2019-05-03 criteria provided, single submitter clinical testing Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31589614, 11139240, 12786748, 24416283, 23647439, 26186295, 22135276, 27743452)

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