Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001070714 | SCV001235982 | uncertain significance | Cystic fibrosis | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 437 of the CFTR protein (p.Gly437Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 19202204, 28544683). ClinVar contains an entry for this variant (Variation ID: 863689). 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 not expected to disrupt CFTR protein function. 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001283963 | SCV001469493 | uncertain significance | not provided | 2020-01-09 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001070714 | SCV002027398 | uncertain significance | Cystic fibrosis | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001070714 | SCV003855890 | uncertain significance | Cystic fibrosis | 2022-11-14 | criteria provided, single submitter | clinical testing | The p.G437D variant (also known as c.1310G>A), located in coding exon 10 of the CFTR gene, results from a G to A substitution at nucleotide position 1310. The glycine at codon 437 is replaced by aspartic acid, an amino acid with similar properties. This alteration was identified with 3849+10kbC>T in an individual diagnosed with cystic fibrosis that was pancreatic sufficient and had milder lung disease (Kolesár P et al. Gen Physiol Biophys, 2008 Dec;27:299-305). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001070714 | SCV001456068 | uncertain significance | Cystic fibrosis | 2020-09-16 | no assertion criteria provided | clinical testing |