Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001838358 | SCV001224958 | pathogenic | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2019-05-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in APOB are known to be pathogenic (PMID: 20032471). This variant has been observed to segregate with familial hypobetalipoproteinaemia in families (PMID: 15805152). This variant is also described as Q1309X in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1336*) in the APOB gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002374949 | SCV002625366 | pathogenic | Cardiovascular phenotype | 2020-08-20 | criteria provided, single submitter | clinical testing | The p.Q1336* pathogenic mutation (also known as c.4006C>T), located in coding exon 25 of the APOB gene, results from a C to T substitution at nucleotide position 4006. This changes the amino acid from a glutamine to a stop codon within coding exon 25. This mutation (also described as p.Q1309* or p.Q1309X) has been detected in multiple individuals with familial hypobetalipoproteinemia, including some compound heterozygotes who have another alteration in APOB (p.R3527Q, c.10580G>A) (Fouchier SW et al. J. Med. Genet., 2005 Apr;42:e23; Huijgen R et al. Hum. Mutat., 2012 Feb;33:448-55). Co-segregation has also been reported in several affected family members (Fouchier SW et al. J. Med. Genet., 2005 Apr;42:e23; Huijgen R et al. Hum. Mutat., 2012 Feb;33:448-55). In addition to the clinical data presented in the literature, 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. |