ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3897A>G (p.Thr1299=) (rs1800131)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000590053 SCV000602975 benign not provided 2017-06-06 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000150339 SCV000110872 likely benign not specified 2017-01-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590053 SCV000696999 benign not provided 2016-10-24 criteria provided, single submitter clinical testing Variant summary: The CFTR c.3897A>G (p.Thr1299Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 141/121634 control chromosomes (1 homozygote) at a frequency of 0.0011592, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603), however the homozygous occurrence does suggest a benign role of the variant. In the literature, the variant is reported in both control and patient populations across multiple ethnicities. However, genotypic information of the patients carrying the variant is not clearly specified in publications, and most of them classify it as a 'polymorphism.' One LabCorp specimen carries F508del (DV) and c.1021T>C (DV) (phase of the variants unknown) and the clinical representation of the pt is reported to be CF. In addition, UMD classifies the variant as a polymorphism that is reported in 5 patients (CF or CBAVD), each carrying two other deleterious variants. Although phase of the two deleterious variants is not reported for every patient, UMD cites 2 CF patients that carry p.Lys710X in cis with p.Thr1299Thr. Thus, we have a unequivocal evidence of the presence of deleterious variant(s) in cis with this silent variant in CF patients, suggesting a notion that it is not causally related to these phenotypes and is likely to be a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as benign.
Invitae RCV000204557 SCV000260695 benign Cystic fibrosis 2017-12-24 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150339 SCV000197442 likely benign not specified 2013-02-21 criteria provided, single submitter clinical testing Thr1299Thr in exon 24 of CFTR: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.1% (10/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800131).
PreventionGenetics RCV000150339 SCV000304495 likely benign not specified criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000150339 SCV000601111 benign not specified 2017-06-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590053 SCV000888092 benign not provided 2017-06-12 criteria provided, single submitter clinical testing

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