ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.216G>A (p.Val72=) (rs151045328)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824776 SCV000064958 pathogenic Rare genetic deafness 2012-04-30 criteria provided, single submitter clinical testing The c.216G>A variant in USH1C has been reported in the homozygous or compound he terozygous state in at least 70 individuals with Usher syndrome (Roux 2011, Bitn er-Glindzicz 2000, DeAngelis 2001, Ebermann 2007, Lentz 2007, Lentz 2005, Lentz 2010, Ouyang 2003, Savas 2002, Zwaenepoel 2001). The variant has been shown to c reate a cryptic splice site and produce a 35-bp deletion in the RNA transcript i n lymphoblasts. This 35-bp deletion leads to a frameshift and premature terminat ion codon 189 bases downstream. In summary, this variant meets criteria to be cl assified as pathogenic for autosomal recessive Usher syndrome.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724016 SCV000229080 pathogenic not provided 2014-06-27 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763237 SCV000893870 pathogenic Usher syndrome, type 1C; Deafness, autosomal recessive 18; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000724016 SCV001223706 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing This sequence change affects codon 72 of the USH1C mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the USH1C protein. This variant is present in population databases (rs151045328, ExAC 0.008%). This variant has been reported in many individuals affected with Usher syndrome 1C (PMID: 15660226, 15578223, 11810303, 17407589) and is considered a founder mutation in the Acadian population (PMID: 17407589, 18665195). ClinVar contains an entry for this variant (Variation ID: 5143). Experimental studies have shown that this silent change introduces a cryptic splice site, resulting in a frameshift and premature protein truncation (PMID: 10973248, 15578223). Furthermore, this variant recapitulates disease in a mouse knock-in model (PMID: 20095043, 23380860). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000724016 SCV001779205 pathogenic not provided 2020-02-17 criteria provided, single submitter clinical testing cDNA analysis demonstrated that the c.216 G>A variant creates a new splice site and results in an out-of-frame deletion of 35 nucleotides (Bitner Glindzicz et al., 2000; Lentz et al., 2005); This variant is associated with the following publications: (PMID: 32581362, 29276601, 11810303, 21436283, 11139240, 17407589, 10973248, 15578223, 23380860, 12630964, 21228398, 28041643)
OMIM RCV000005450 SCV000025632 pathogenic Usher syndrome, type 1C 2002-01-01 no assertion criteria provided literature only
GeneReviews RCV000005450 SCV000086931 pathologic Usher syndrome, type 1C 2013-06-20 no assertion criteria provided curation Converted during submission to Pathogenic.
GeneReviews RCV000220605 SCV000268750 pathogenic Usher syndrome type 1 2016-05-19 no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504855 SCV000598661 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research
Counsyl RCV000984012 SCV000789704 likely pathogenic Deafness, autosomal recessive 18 2017-02-14 no assertion criteria provided clinical testing

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