ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4723A>T (p.Lys1575Ter) (rs137852834)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program,University of Washington RCV000001402 SCV000256371 pathogenic Joubert syndrome 5 2015-02-23 criteria provided, single submitter research
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415219 SCV000492731 pathogenic Blindness 2015-02-02 criteria provided, single submitter clinical testing
GeneDx RCV000484693 SCV000567332 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing The K1575X nonsense variant has been previously reported in individuals with Joubert syndrome, Senior-Loken syndrome (SLS), and non-syndromic Leber congenital amaurosis, who all harbored a secondCEP290 variant on the other allele (Brancati et al., 2007, Perrault et al., 2007). Additionally, K1575X ishypothesized to represent a founder variant from France (Perrault et al., 2007). This variant ispredicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we consider K1575X in CEP290 to be a pathogenic variant.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000508230 SCV000602965 pathogenic not specified 2017-03-08 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763312 SCV000893989 pathogenic Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 2018-10-31 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV001002715 SCV001156391 pathogenic Senior-Loken syndrome 6 2019-02-01 criteria provided, single submitter clinical testing
Invitae RCV001046610 SCV001210519 pathogenic Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1575*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs137852834, ExAC 0.03%). This variant has been observed to be homozygous and/or in combination with another CEP290 variant in several individuals affected with CEP290-related disorders (PMID: 28497568, 17345604, 20683928, 28829391, 26092869, 25920555, 29398085, 23188109). ClinVar contains an entry for this variant (Variation ID: 1339). Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001075829 SCV001241466 pathogenic Retinal dystrophy 2019-07-25 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196407 SCV001367015 pathogenic Behavioral abnormality; Slurred speech; Progressive gait ataxia; Movement disorder 2020-01-08 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3. This variant was detected in heterozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197646 SCV001368425 pathogenic Congenital blindness; Absent speech; Muscular hypotonia 2020-02-24 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. This variant was detected in heterozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198271 SCV001369150 pathogenic Nystagmus; Abnormal retinal morphology; Molar tooth sign on MRI; Central hypotonia 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. This variant was detected in homozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198980 SCV001369975 pathogenic Retinal dystrophy; Abnormality of vision 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3. This variant was detected in heterozygous state.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001199376 SCV001370479 pathogenic Abnormal heart morphology; Blindness 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. This variant was detected in heterozygous state.
OMIM RCV000001402 SCV000021552 pathogenic Joubert syndrome 5 2007-07-01 no assertion criteria provided literature only
OMIM RCV000001403 SCV000021553 pathogenic Leber congenital amaurosis 10 2007-07-01 no assertion criteria provided literature only
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415120 SCV000492659 pathogenic Nystagmus; Molar tooth sign on MRI; Central hypotonia 2016-03-07 no assertion criteria provided clinical testing

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