Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479512 | SCV000572377 | likely pathogenic | not provided | 2016-11-23 | criteria provided, single submitter | clinical testing | The c.128_144del17ins28 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.128_144del17ins28 variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.128_144del17ins28 variant causes a frameshift starting with codon Proline 43, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Pro43LeufsX3. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret this variant to be likely pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509407 | SCV002819603 | likely pathogenic | Holocarboxylase synthetase deficiency | 2022-12-16 | criteria provided, single submitter | clinical testing | Variant summary: HLCS c.128_144delinsTTGCTTGAGATTAAGCCTGAGATTAAGG (p.Pro43LeufsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249914 control chromosomes (gnomAD). To our knowledge, no occurrence of c.128_144delins28 in individuals affected with Holocarboxylase Synthetase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002509407 | SCV005664108 | likely pathogenic | Holocarboxylase synthetase deficiency | 2024-04-16 | criteria provided, single submitter | clinical testing |