Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000007618 | SCV000886280 | pathogenic | Cystic fibrosis | 2018-11-05 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000007618 | SCV001574747 | pathogenic | Cystic fibrosis | 2023-03-03 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 109 of the CFTR protein (p.Tyr109Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 7524909, 27022295, 30232781, 30558651). 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: 7197). 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. Experimental studies have shown that this missense change affects CFTR function (PMID: 11278813). This variant disrupts the p.Tyr109 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32539862). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003473040 | SCV004213358 | likely pathogenic | Bronchiectasis with or without elevated sweat chloride 1 | 2023-09-27 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000007618 | SCV004241705 | pathogenic | Cystic fibrosis | 2023-12-27 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.326A>G (p.Tyr109Cys) results in a non-conservative amino acid change located in the first transmembrane region (IPR011527) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251116 control chromosomes (gnomAD). c.326A>G has been reported in the literature in multiple compound heterozygous individuals who carried a pathogenic variant in trans and were affected with Cystic Fibrosis (e.g. Schaedel_1995, Sanchez_2016, Shen_2016). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and demonstrated decreased channel activity compared to the wild-type (Hammerle_2001). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000007618 | SCV000027819 | pathogenic | Cystic fibrosis | 2018-04-09 | no assertion criteria provided | literature only |