ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs527236117
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Total submissions: 5
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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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001378479 SCV001576051 pathogenic not provided 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 117 of the TULP1 protein (p.Glu117Lys). This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with retinitis pigmentosa (PMID: 25324289, 33691693). ClinVar contains an entry for this variant (Variation ID: 143126). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt 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. For these reasons, this variant has been classified as Pathogenic.
3billion, Medical Genetics RCV001376329 SCV002318695 likely pathogenic Retinitis pigmentosa 14 2022-03-22 criteria provided, single submitter clinical testing Same or different nucleotide change resulting in same amino acid change has been previously reported to be associated with TULP1 related disorder (PMID:25324289). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual(PMID: 25324289). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000094). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Fulgent Genetics, Fulgent Genetics RCV005031648 SCV005671273 likely pathogenic Retinitis pigmentosa 14; Leber congenital amaurosis 15 2024-03-29 criteria provided, single submitter clinical testing
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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