Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001378676 | SCV001576299 | uncertain significance | Hereditary pancreatitis | 2023-06-04 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1067420). This variant has not been reported in the literature in individuals affected with CTRC-related conditions. This variant is present in population databases (rs151102347, gnomAD 0.004%). This sequence change affects a donor splice site in intron 4 of the CTRC 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), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CTRC cause disease. |
Ambry Genetics | RCV001378676 | SCV002616640 | uncertain significance | Hereditary pancreatitis | 2022-02-17 | criteria provided, single submitter | clinical testing | The c.356+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 4 of the CTRC gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |