ClinVar Miner

Submissions for variant NM_005709.3(USH1C):c.238dupC (p.Arg80Profs) (rs397515359)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824775 SCV000064967 pathogenic Rare genetic deafness 2015-07-26 criteria provided, single submitter clinical testing The p.Arg80fs variant in USH1C has been reported as a homozygous variant in at l east 5 individuals and as a compound heterozygous variant in at least 8 individu als with Usher syndrome, was absent in 552 control chromosomes, and segregated w ith a second pathogenic variant in 5 affected siblings (Bitner-Glindzicz 2000, B laydon 2003, Ebermann 2007, Le Quesne Stabej 2012, Ouyang 2003, Verpy 2000, Zwae nepoel 2001). It has been identified in 35/64768 European chromosomes by the Ex ome Aggregation Consortium (ExAC,; dbSNP rs148597 739); however, its frequency is low enough to be consistent with a recessive car rier frequency. This frameshift variant is predicted to alter the protein?s amin o acid sequence beginning at position 80 and lead to a premature termination cod on 69 amino acids downstream. This alteration is then predicted to lead to a tru ncated or absent protein. In summary, this variant meets our criteria to be clas sified as pathogenic for autosomal recessive Usher syndrome.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727619 SCV000854885 pathogenic not provided 2017-11-28 criteria provided, single submitter clinical testing
Invitae RCV000727619 SCV000948241 pathogenic not provided 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg80Profs*69) in the USH1C gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs397515359, ExAC 0.05%). This variant has been reported as homozygous or compound heterozygous in families and individuals affected with Usher syndrome type I (PMID: 10973248, 26969326, 12702164, 17407589). ClinVar contains an entry for this variant (Variation ID: 5141). 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.
Baylor Genetics RCV000213574 SCV001163634 pathogenic Usher syndrome type 1 criteria provided, single submitter clinical testing
Laboratory of Prof. Karen Avraham,Tel Aviv University RCV000005448 SCV001164299 pathogenic Usher syndrome, type 1C 2018-05-07 criteria provided, single submitter research Recessive, congenital, profound HL;USH1C
GeneDx RCV000727619 SCV001168546 pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing The c.238dupC variant in the USH1C gene has been published previously as a homozygous variant in association with Usher syndrome (Bitner-Glindzicz et al., 2000). The duplication causes a frameshift starting with codon Arginine 80, changes this amino acid to a Proline residue and creates a premature Stop codon at position 69 of the new reading frame, denoted p.Arg80ProfsX69. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.238dupC variant is observed in 12/30952 (0.0388%) alleles in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Myriad Women's Health, Inc. RCV000005448 SCV001194110 pathogenic Usher syndrome, type 1C 2019-12-17 criteria provided, single submitter clinical testing NM_153676.3(USH1C):c.238dupC(R80Pfs*69) is classified as pathogenic in the context of USH1C-related disorders. Sources cited for classification include the following: PMID 10973248 and 11139240. Classification of NM_153676.3(USH1C):c.238dupC(R80Pfs*69) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.
Blueprint Genetics RCV001073457 SCV001238999 pathogenic Retinal dystrophy 2019-02-27 criteria provided, single submitter clinical testing
OMIM RCV000005448 SCV000025630 pathogenic Usher syndrome, type 1C 2001-01-01 no assertion criteria provided literature only
GeneReviews RCV000005448 SCV000086932 pathologic Usher syndrome, type 1C 2013-06-20 no assertion criteria provided curation Converted during submission to Pathogenic.
GeneReviews RCV000213574 SCV000268751 pathogenic Usher syndrome type 1 2016-05-19 no assertion criteria provided literature only
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505081 SCV000598662 pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research
Counsyl RCV000984011 SCV000678126 pathogenic Deafness, autosomal recessive 18 2017-01-03 no assertion criteria provided clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787893 SCV000926909 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV000213574 SCV001161326 pathogenic Usher syndrome type 1 2019-06-23 no assertion criteria provided research

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