ClinVar Miner

Submissions for variant NM_014053.4(FLVCR1):c.1092+5G>A (rs556788423)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415829 SCV000493676 pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing
GeneDx RCV000415829 SCV000577806 likely pathogenic not provided 2018-05-21 criteria provided, single submitter clinical testing The c.1092+5G>A variant in the FLVCR1 gene has been reported previously in individuals with nonsyndromic retinitis pigmentosa when present in the homozygous state or when present with another disease-causing FLVCR1 variant (Glockle et al., 2014; Tiwari et al., 2016; Yusuf et al., 2018). This variant reduces the quality of the splice donor site in intron 4, and in vitro functional studies demonstrate abnormal gene splicing (Tiwari et al., 2016). The c.1092+5G>A variant is observed in 65/263,396 (0.0247%) global alleles in large population cohorts and no individuals were reported to be homozygous (Lek et al., 2016). We interpret c.1092+5G>A as a likely pathogenic variant.
Mendelics RCV000986509 SCV001135524 likely pathogenic Posterior column ataxia-retinitis pigmentosa syndrome 2019-05-28 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001075766 SCV001241398 pathogenic Retinal dystrophy 2019-06-25 criteria provided, single submitter clinical testing
Invitae RCV000415829 SCV001409598 pathogenic not provided 2019-10-29 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the FLVCR1 gene. It does not directly change the encoded amino acid sequence of the FLVCR1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs556788423, ExAC 0.04%). This variant has been reported in the homozygous or compound heterozygous state in individuals affected with retinitis pigmentosa (PMID: 23591405, 27353947). ClinVar contains an entry for this variant (Variation ID: 374768). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this splice site change results in the skipping of exon 4, which is predicted to introduce a premature terminate codon (PMID: 27353947). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000415829 SCV001446625 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000415829 SCV001713133 likely pathogenic not provided 2020-10-12 criteria provided, single submitter clinical testing PS3, PS4_moderate, PM2, PP3

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