ClinVar Miner

Submissions for variant NM_020458.4(TTC7A):c.793C>T (p.Arg265Trp)

gnomAD frequency: 0.00003  dbSNP: rs150269540
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
NIHR Bioresource Rare Diseases, University of Cambridge RCV001027641 SCV001190213 pathogenic Common variable immunodeficiency 2019-01-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001367045 SCV001563377 uncertain significance Multiple gastrointestinal atresias 2021-09-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 265 of the TTC7A protein (p.Arg265Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs150269540, ExAC 0.001%). This missense change has been observed in individual(s) with clinical features of TTC7A-related conditions (PMID: 32499645). ClinVar contains an entry for this variant (Variation ID: 827752). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526797 SCV005039864 uncertain significance not specified 2024-03-18 criteria provided, single submitter clinical testing Variant summary: TTC7A c.793C>T (p.Arg265Trp) results in a non-conservative amino acid change located in the Tetratricopeptide repeat protein 7, N-terminal domain (IPR045819) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251480 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.793C>T has been reported in the literature in at least one compound heterozygous individual affected with Severe Combined Immunodeficiency (e.g., Thavaenthiran_2020, Maimaris_2020 (no PMID)). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 32499645). ClinVar contains an entry for this variant (Variation ID: 827752). Based on the evidence outlined above, the variant was classified as uncertain significance.

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