Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000483714 | SCV000566467 | pathogenic | not provided | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant is denoted SDHA c.1526_1527delCGinsGA at the cDNA level and p.Ser509Ter (S509X) at the protein level. The surrounding sequence is ACAT[delCG][insGA]GAAC. This in frame deletion and insertion of 2 nucleotides creates a nonsense variant, which changes a Serine to a premature stop codon. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider SDHA c.1526_1527delCGinsGA to be pathogenic. |
| Ambry Genetics | RCV000575106 | SCV000675026 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-11-25 | criteria provided, single submitter | clinical testing | The c.1526_1527delCGinsGA pathogenic mutation, located in coding exon 11 of the SDHA gene, results from an in-frame deletion of CG and insertion of GA at nucleotide positions 1526 to 1527. This changes the amino acid from a serine to a stop codon within coding exon 11 (p.S509*). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV000800769 | SCV000940501 | pathogenic | Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser509*) in the SDHA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHA are known to be pathogenic (PMID: 22974104, 24781757). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 418987). For these reasons, this variant has been classified as Pathogenic. |
| Prevention |
RCV003401517 | SCV004110297 | pathogenic | SDHA-related condition | 2023-04-07 | criteria provided, single submitter | clinical testing | The SDHA c.1526_1527delinsGA variant is predicted to result in premature protein termination (p.Ser509*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in SDHA are expected to be pathogenic. This variant is interpreted as pathogenic. |
| Baylor Genetics | RCV003476157 | SCV004200642 | likely pathogenic | Dilated cardiomyopathy 1GG | 2023-05-24 | criteria provided, single submitter | clinical testing |