Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000043621 | SCV000713180 | likely pathogenic | GAPO syndrome | 2017-05-01 | criteria provided, single submitter | clinical testing | The p.Arg169X (NM_032208.2 c.505C>T) variant in ANTXR1 has been reported in 1 ho mozygous individual with growth delay alopecia pseudoanodontia-optic atrophy syn drome (GAPO) (Stranecky 2013), and was absent from large population studies. Cel l lines from this published case provide evidence supporting that this variant c auses GAPO syndrome (reduced RT-PCR products, reductions in relative cDNA expres sion, absence of protein from skin fibroblasts by immunoblot, and alterations in actin cytoskeleton network by immunofluorescence) (Stranecky 2013). This nonsen se variant leads to a premature termination codon at position 169, which is pred icted to lead to a truncated or absent protein. Biallelic loss of function of th e ANTXR1 gene has been associated with GAPO syndrome. In summary, the p.Arg169X variant in ANTXR1 gene is likely pathogenic for GAPO syndrome in an autosomal r ecessive manner based on case report, absence in controls and functional evidenc e. |
| Labcorp Genetics |
RCV005089405 | SCV005834822 | pathogenic | not provided | 2024-11-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg169*) in the ANTXR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANTXR1 are known to be pathogenic (PMID: 23602711). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with growth retardation, alopecia, pseudoanodontia and progressive optic atrophy syndrome (PMID: 23602711). ClinVar contains an entry for this variant (Variation ID: 50906). 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. |
| OMIM | RCV000043621 | SCV000071646 | pathogenic | GAPO syndrome | 2013-05-02 | no assertion criteria provided | literature only |