Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471740 | SCV002766643 | uncertain significance | Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome | 2020-05-01 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as a 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. Both NMD-predicted and missense variants have been reported to have loss of function effects (OMIM; PMID 27666374; PMID 27666370). (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from a glycine to a serine (exon 29). (N) 0251 - Variant is heterozygous. (N) 0301 - Variant is absent from gnomAD. (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (1 heterozygote, 0 homozygotes). (N) 0503 - Missense variant consistently predicted to be tolerated or not conserved in mammals with a minor amino acid change. (B) 0504 - Same amino acid change has been observed in mammals. (N) 0600 - Variant is located in an annotated domain or motif (TFCD C super family; NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant in the literature. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is maternally inherited (identified by external laboratory). (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |