Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000190635 | SCV000245676 | pathogenic | Familial isolated deficiency of vitamin E | 2014-12-22 | criteria provided, single submitter | clinical testing | The p.Gln7SerfsX64 variant in TTPA has not been previously reported in individuals with disease but has been identified in 0.016% (1/6134) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 7 and leads to a premature termination codon 64 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Homozygous or compound heterozygous loss of function variants in TTPA have been shown to cause ataxia with isolated vitamin E deficiency. In summary, this variant meets our criteria to be classified as pathogenic for ataxia with isolated vitamin E deficiency in an autosomal recessive manner. |
| Labcorp Genetics |
RCV001047609 | SCV001211576 | pathogenic | not provided | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln7Serfs*64) in the TTPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TTPA are known to be pathogenic (PMID: 9463307, 26068213). This variant is present in population databases (rs760014795, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with TTPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 208623). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000190635 | SCV004207490 | likely pathogenic | Familial isolated deficiency of vitamin E | 2024-03-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004678637 | SCV005180172 | pathogenic | Inborn genetic diseases | 2024-06-13 | criteria provided, single submitter | clinical testing | The c.19delC (p.Q7Sfs*64) alteration, located in exon 1 (coding exon 1) of the TTPA gene, consists of a deletion of one nucleotide at position 19, causing a translational frameshift with a predicted alternate stop codon after 64 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, this allele has an overall frequency of 0.004% (6/135078) total alleles studied. The highest observed frequency was <0.001% (6/6848) of Ashkenazi Jewish alleles. Based on the available evidence, this alteration is classified as pathogenic. |