Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV003329210 | SCV004035994 | uncertain significance | Mitochondrial disease | 2023-02-06 | criteria provided, single submitter | clinical testing | The ATPF51A c.326T>C (p.Leu109Ser) missense variant results in the substitution of leucine at amino acid position 109 with serine. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is not found in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Multiple lines of computational evidence suggest the variant may have a deleterious effect on the gene or gene product. This variant was identified in a de novo state. Based on the available evidence, the c.326T>C (p.Leu109Ser) variant is classified as a variant of uncertain significance for primary mitochondrial disease. |
Ambry Genetics | RCV004686773 | SCV005173246 | likely pathogenic | Inborn genetic diseases | 2024-04-18 | criteria provided, single submitter | clinical testing | The c.326T>C (p.L109S) alteration is located in exon 5 (coding exon 4) of the ATP5F1A gene. This alteration results from a T to C substitution at nucleotide position 326, causing the leucine (L) at amino acid position 109 to be replaced by a serine (S). for autosomal dominant ATP5F1A-related mitochondrial complex V deficiency; however, its clinical significance for autosomal recessive ATP5F1A-related mitochondrial complex V deficiency is uncertain This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Another alteration at the same codon, c.327G>C (p.L109F), has been detected de novo in one individual with clinical features consistent with ATP5F1A-related mitochondrial complex V deficiency (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |