Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000665515 | SCV000789653 | uncertain significance | Cystic fibrosis | 2017-02-16 | criteria provided, single submitter | clinical testing | |
CFTR- |
RCV001009540 | SCV001169635 | pathogenic | Cystic fibrosis; CFTR-related disorders | 2018-03-09 | criteria provided, single submitter | curation | the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both |
Genome- |
RCV000665515 | SCV001822085 | likely pathogenic | Cystic fibrosis | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000665515 | SCV002279240 | pathogenic | Cystic fibrosis | 2023-07-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 26277102). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 604 of the CFTR protein (p.Thr604Ile). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 53395). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. This variant disrupts the p.Thr604 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been observed in individuals with CFTR-related conditions (PMID: 15858154, 26277102; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |