Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000300236 | SCV000342707 | uncertain significance | not provided | 2016-06-23 | criteria provided, single submitter | clinical testing | |
| CFTR- |
RCV001009485 | SCV001169580 | pathogenic | CFTR-related disorders | 2018-01-29 | criteria provided, single submitter | curation | |
| Invitae | RCV001852982 | SCV002170632 | pathogenic | Cystic fibrosis | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1377 of the CFTR protein (p.Asp1377His). This variant is present in population databases (rs150683293, gnomAD 0.0009%). This missense change has been observed in individual(s) with CFTR-related conditions (PMID: 8556303, 9239681, 9272157). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53896). 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. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003488366 | SCV004241757 | uncertain significance | not specified | 2023-12-04 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.4129G>C (p.Asp1377His) results in a non-conservative amino acid change located in the ATP-binding domain (IPR003439) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251184 control chromosomes (gnomAD). c.4129G>C has been reported in the literature in individuals affected with Congenital Bilateral Absence Of The Vas Deferens (e.g. Costes_1995, DeBraekeleer_1996, Dork_1997, Steiner_2011). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 8556303, 9239681, 9272157, 21520337, 34405919). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as VUS (n=2) or pathogenic (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |