Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000728855 | SCV000856473 | uncertain significance | not provided | 2017-08-18 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330924 | SCV004037678 | likely pathogenic | Peroxisome biogenesis disorder | 2023-08-29 | criteria provided, single submitter | clinical testing | Variant summary: PEX6 c.1231A>G (p.Met411Val) results in a conservative amino acid change in the encoded protein sequence and is close to the canonical splice site of Intron 4. Five of five in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251484 control chromosomes. c.1231A>G has been reported in the literature at a compound heterozygous state along with a pathogenic frame-shifting variant in multiple individuals affected with hearing loss from a single family (example, Marino_2022). These data indicate that the variant is likely to be associated with Zellweger Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function and no other case-level evidence have been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34387732). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 (likely pathogenic, n=1; uncertain significance, n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Prevention |
RCV003396305 | SCV004104028 | uncertain significance | PEX6-related condition | 2022-11-10 | criteria provided, single submitter | clinical testing | The PEX6 c.1231A>G variant is predicted to result in the amino acid substitution p.Met411Val. This variant has been reported to segregate with hearing loss in the compound heterozygous state along with a pathogenic variant in seven patients from a single family without other features of Zellweger syndrome (Cruz Marino et al 2022. PubMed ID: 34387732). However, phase of these variants was not conclusively established. This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-42937625-T-C). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Service de Biologie Medicale, |
RCV001786416 | SCV001712143 | likely pathogenic | Heimler syndrome 2 | 2020-07-31 | no assertion criteria provided | clinical testing |