ClinVar Miner

Submissions for variant NM_033100.4(CDHR1):c.783G>A (p.Pro261=) (rs147346345)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000369498 SCV000365411 uncertain significance Cone-Rod Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487554 SCV000574853 likely pathogenic not provided 2017-04-30 criteria provided, single submitter clinical testing
GeneDx RCV000487554 SCV000617830 uncertain significance not provided 2017-07-31 criteria provided, single submitter clinical testing The c.783 G>A variant in the CDHR1 gene has been reported in the compound heterouzygous state in a a patient with sporadic retinitis pigmentosa (Glockle et al., 2014). The c.783 G>A variant is observed in 376/66728 (0.5%) alleles from individuals of non-Finnish European background in the ExAC dataset, including one homozygote (Lek et al., 2016). Although the c.783 G>A (P261=) variant results in a synonymous amino acid substitution, splice algorithms predict this variant destroys the natural splice donor site in intron 8, which may lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of c.783 G>A in this individual is unknown. We interpret c.783 G>A as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000487554 SCV000701570 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000625429 SCV000745341 uncertain significance Cone-rod dystrophy 15 2017-06-28 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825304 SCV000966599 uncertain significance not specified 2018-12-19 criteria provided, single submitter clinical testing The c.783G>A (p.Pro261Pro) variant in CDHR1 has been reported in 3 homozygous an d 3 compound heterozygous individuals with retinitis pigmetosa, as well as a het erozygous variant in one individual with an altenative cause of disease (Glockle 2013, Tiwari 2016, Haer-Wigman 2017, Stingl 2017, Bessette 2018). This variant has been identified in 0.6% (148/25122) of Finnish chromosomes, including 3 homo zygotes, by gnomAD (http://gnomad.broadinstitute.org).This variant is located in the last base of the exon, which is part of the 5? splice region. Computational tools suggest an impact to splicing; however, this information is not predictiv e enough to determine pathogenicity. Funcitonal studies suggest this variant lea ds to skipping of exon 8; however, these assays may not accurately represent bio logical function. In summary, due to conflicting data, the clinical significance of the p.Pro261Pro variant is uncertain. ACMG/AMP criteria applied: PM3, PS4_Mo derate, PS3_Supporting, BS1_Supporting, BP5.
Invitae RCV000487554 SCV001038155 benign not provided 2018-08-20 criteria provided, single submitter clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787811 SCV000926821 likely pathogenic Retinal dystrophy 2018-04-01 no assertion criteria provided research

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