ClinVar Miner

Submissions for variant NM_020458.4(TTC7A):c.1364C>T (p.Ala455Val)

gnomAD frequency: 0.00003  dbSNP: rs201913059
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000810997 SCV000951240 uncertain significance Multiple gastrointestinal atresias 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 455 of the TTC7A protein (p.Ala455Val). 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 variant has not been reported in the literature in individuals affected with TTC7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 654925). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TTC7A protein function. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV000810997 SCV002072949 uncertain significance Multiple gastrointestinal atresias criteria provided, single submitter clinical testing The missense variant p.A455V in TTC7A (NM_020458.4) has been submitted to ClinVar as a Variant of Uncertain Significance.The variant has not been reported in literature in affected individuals. The p.A455V variant is observed in 5/1,13,152 (0.0044%) alleles from individuals of European (Non-Finnish) background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. In silico tools are contradictory in their predictions (SIFT-tolerated, Polyphen-Damaging) and the residue is conserved across species. For these reasons, this variant has been classified as Uncertain Significance.

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