ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.328G>C (p.Asp110His) (rs113993958)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000007527 SCV000071497 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
PharmGKB RCV000660769 SCV000783008 drug response ivacaftor response - Efficacy 2018-03-22 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
Counsyl RCV000007527 SCV000220934 likely pathogenic Cystic fibrosis 2014-12-05 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780153 SCV000917200 pathogenic not specified 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The CFTR c.328G>C (p.Asp110His) variant involves the alteration of a conserved nucleotide that is located in the ABC transporter type 1, transmembrane domain (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 5/245956 control chromosomes at a frequency of 0.0000203, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). Compound heterozygotes and homozygotes for this variant have been found in numerous patients with CBAVD, CF, and in pt with clinical findings suggestive of CF. A functional study showed that baseline chloride transport in CFTR-D110H transfected FRT cells was 9.1% of that in WT-CFTR transfected FRT cells (Van Goor_2013), indicating that D110H significantly affects normal function of CFTR. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV001004427 SCV001163471 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
CFTR-France RCV001009392 SCV001169245 pathogenic Cystic fibrosis; CFTR-related disorders 2018-01-29 criteria provided, single submitter curation when the variant is in trans with another CF-causing variation, can either result in CF or in a CFTR-RD
Invitae RCV000007527 SCV001589600 pathogenic Cystic fibrosis 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 110 of the CFTR protein (p.Asp110His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs113993958, ExAC 0.005%). This variant has been reported in individuals affected with cystic fibrosis (PMID: 2344617, 22724884, 23974870, 18373402, 20059485), congenital bilateral absence of the vas deferens (PMID: 20949073, 9272157, 19897426), and infertility (PMID: 19897426). ClinVar contains an entry for this variant (Variation ID: 7108). Experimental studies have shown that this missense change impairs CFTR chloride ion transport (PMID: 23891399, 11278813). For these reasons, this variant has been classified as Pathogenic.
Nilou-Genome Lab RCV000007527 SCV001810353 pathogenic Cystic fibrosis 2021-07-22 criteria provided, single submitter clinical testing
OMIM RCV000007527 SCV000027728 pathogenic Cystic fibrosis 1991-01-01 no assertion criteria provided literature only
SNPedia RCV000058930 SCV000090451 not provided not provided no assertion provided not provided

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