ClinVar Miner

Submissions for variant NM_003322.6(TULP1):c.349G>A (p.Glu117Lys) (rs527236117)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ocular Genomics Institute, Massachusetts Eye and Ear RCV001376329 SCV001573437 uncertain significance Retinitis pigmentosa 14 2021-04-08 criteria provided, single submitter research The TULP1 c.349G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.
Invitae RCV001378479 SCV001576051 likely pathogenic not provided 2020-02-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 117 of the TULP1 protein (p.Glu117Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant also falls at the last nucleotide of exon 4 of the TULP1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 25324289, Invitae). ClinVar contains an entry for this variant (Variation ID: 143126). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Not Available; PolyPhen-2: Benign; Align-GVGD: Not Available). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132650 SCV000172601 probable-pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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