ClinVar Miner

Submissions for variant NM_025103.4(IFT74):c.902C>T (p.Pro301Leu)

gnomAD frequency: 0.00052  dbSNP: rs78753648
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001947597 SCV002175948 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 301 of the IFT74 protein (p.Pro301Leu). This variant is present in population databases (rs78753648, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with IFT74-related conditions. ClinVar contains an entry for this variant (Variation ID: 1401716). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
New York Genome Center RCV002468346 SCV002764467 uncertain significance Joubert syndrome 40; Spermatogenic failure 58 2021-11-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002554365 SCV003694015 uncertain significance Inborn genetic diseases 2021-06-18 criteria provided, single submitter clinical testing The c.902C>T (p.P301L) alteration is located in exon 11 (coding exon 10) of the IFT74 gene. This alteration results from a C to T substitution at nucleotide position 902, causing the proline (P) at amino acid position 301 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003416562 SCV004116921 uncertain significance IFT74-related disorder 2024-09-20 no assertion criteria provided clinical testing The IFT74 c.902C>T variant is predicted to result in the amino acid substitution p.Pro301Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.098% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, which may be too frequent to be a primary cause of disease. Although we suspect that this variant may be benign, the clinical significance of this variant is currently classified as uncertain due to the absence of conclusive functional and genetic evidence.

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