Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000456955 | SCV000553858 | pathogenic | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-10-31 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 6 (c.762_770+17del) of the SDHA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individual(s) with metastatic paraganglioma (PMID: 32688340). ClinVar contains an entry for this variant (Variation ID: 412346). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002393168 | SCV002673777 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-15 | criteria provided, single submitter | clinical testing | The c.762_770+17del26 variant results from a deletion of 26 nucleotides from nucleotide position 762 to 770+17 and involves the canonical splice donor site after coding exon 6 of the SDHA gene. This alteration was identified in an individual with a paraganglioma diagnosed at age 19 (Main Am et al. Endocr Connect, 2020 Aug;9(8):793-803). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The canonical splice donor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
Fulgent Genetics, |
RCV002506134 | SCV002809844 | likely pathogenic | Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy | 2021-10-16 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV003316574 | SCV004020101 | likely pathogenic | Paragangliomas 5 | 2023-02-13 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
Baylor Genetics | RCV003476122 | SCV004200658 | likely pathogenic | Dilated cardiomyopathy 1GG | 2023-03-28 | criteria provided, single submitter | clinical testing |