ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1054C>T (p.Arg352Trp) (rs193922497)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000664320 SCV000603070 pathogenic Hereditary pancreatitis 2018-05-15 criteria provided, single submitter clinical testing The CFTR c.1054C>T, p.Arg352Trp variant (rs193922497) is reported in individuals diagnosed with cystic fibrosis (Schrijver 2005), but was found in a complex variant with p.Pro750Leu (McGinniss 2005). It was also reported in a patient with CBAVD, in-trans with p.Phe508del (Picci 2010), and associated with CFTR-related disorders in our own internal clinical database. This variant is found in the Latino population with an allele frequency of 0.3% (104/34386 alleles) in the Genome Aggregation Database. The arginine at residue 352 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that the variant is deleterious. Additionally, another variant in the same codon, p.Arg352Gln, is considered pathogenic (Sosnay 2013). Based on the above information, the variant is classified as pathogenic, with a likely mild phenotype.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727191 SCV000706515 uncertain significance not provided 2017-03-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029469 SCV000916179 uncertain significance Cystic fibrosis 2018-11-06 criteria provided, single submitter clinical testing The CFTR c.1054C>T (p.Arg352Trp) variant is a missense variant that has been reported in at least four studies, in which it is found in a compound heterozygous state with a second variant in four individuals, including in one individual with congenital bilateral absence of the vas deferens and in three newborns who underwent additional screening for cystic fibrosis (CF) following abnormal newborn screening for this condition (McGinniss et al. 2005; Soultan et al. 2008; Lilley et al. 2010; Picci et al. 2010). Two of the newborns were found to carry the p.Arg352Trp variant in cis with another missense variant on one allele and a classic CF variant on the other allele. The CF status of these newborns is not known. Control data are unavailable for this variant, which is reported at a frequency of 0.004764 in the Latino population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Arg352Trp variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for CFTR-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Integrated Genetics/Laboratory Corporation of America RCV000029469 SCV000052119 uncertain significance Cystic fibrosis 2015-10-02 no assertion criteria provided clinical testing
Invitae RCV000029469 SCV000074226 likely benign Cystic fibrosis 2017-12-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506190 SCV000601037 uncertain significance not specified 2017-05-02 criteria provided, single submitter clinical testing

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