Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000791633 | SCV000930891 | pathogenic | not provided | 2024-11-05 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 14 of the MTTP 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 MTTP are known to be pathogenic (PMID: 8533758, 9671739). This variant is present in population databases (rs764189338, gnomAD 0.002%). Disruption of this splice site has been observed in individuals with abetalipoproteinemia (PMID: 8533758, 27578136). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 638950). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532971 | SCV001748795 | pathogenic | Abetalipoproteinaemia | 2021-06-28 | criteria provided, single submitter | clinical testing | Variant summary: MTTP c.1867+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251398 control chromosomes (gnomAD). c.1867+1G>A has been reported in the literature in individuals affected with Abetalipoproteinaemia (Bassen-Kornzweig Syndrome), including one homozygote (Narcisi_1995, Pons_2011, Paquette_2016). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV001532971 | SCV002806660 | pathogenic | Abetalipoproteinaemia | 2024-02-01 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001532971 | SCV002082446 | pathogenic | Abetalipoproteinaemia | 2021-01-26 | no assertion criteria provided | clinical testing |