ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2255T>G (p.Ile752Ser)

gnomAD frequency: 0.00001  dbSNP: rs766541549
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000630459 SCV000751415 uncertain significance Cystic fibrosis 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 752 of the CFTR protein (p.Ile752Ser). This variant is present in population databases (rs766541549, gnomAD 0.005%). This missense change has been observed in individual(s) with atypical chronic rhino-sinusitis and nasal polyposis and no other signs suggestive of cystic fibrosis (PMID: 18493878). ClinVar contains an entry for this variant (Variation ID: 526021). 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 with a negative predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV001311301 SCV001501417 uncertain significance not provided 2020-08-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000630459 SCV002027444 uncertain significance Cystic fibrosis 2021-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV000630459 SCV002736511 likely benign Cystic fibrosis 2022-05-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001834987 SCV002080727 uncertain significance CFTR-related disorder 2018-06-06 no assertion criteria provided clinical testing

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