ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1367T>C (p.Val456Ala) (rs193922500)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000029474 SCV000924258 pathogenic Cystic fibrosis 2017-12-08 reviewed by expert panel research
Counsyl RCV000029474 SCV000486198 likely pathogenic Cystic fibrosis 2016-04-13 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000731635 SCV000859479 likely pathogenic not provided 2018-01-31 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763570 SCV000894409 likely pathogenic Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029474 SCV000916181 pathogenic Cystic fibrosis 2018-09-06 criteria provided, single submitter clinical testing The CFTR c.1367T>C (p.Val456Ala) missense variant has been reported in five studies in which it is found in a total of nine individuals with CFTR-related disorders, including in one in a homozygous state and in eight in a compound heterozygous state (McCormick et al. 2002; Strom et al. 2003; Danziger et al. 2004; Ziedalski et al. 2006; Uppaluri et al. 2012). Three of the compound heterozygotes carried the common p.Phe508del variant on the second allele and four carried the same stop-gained variant on the second allele. One of the compound heterozygotes who presented with only congenital bilateral absence of the vas deferens was compound heterozygous for the p.Val456Ala variant and a 5T allele (a variable repeat located in intron 8 of the CFTR gene considered to be a variably penetrant mutation and to decrease the efficiency of intron 8 splicing) (Danziger et al. 2004). Additionally, Strom et al. (2003) identified the p.Val456Ala variant in a homozygous state in an asymptomatic proband suggesting that this is a mild allele. Control data are unavailable for this variant, which is reported at a frequency of 0.00306 in the South Asian population of the 1000 Genomes Project. The reported cases suggest the variant is more likely to lead to a classic cystic fibrosis phenotype when inherited in compound heterozygous state with a severe allele. Based on the evidence from the literature, the p.Val456Ala variant is classified as pathogenic 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 RCV000029474 SCV000052124 likely pathogenic Cystic fibrosis 2015-10-02 no assertion criteria provided clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000731635 SCV000889282 pathogenic not provided 2018-07-11 criteria provided, single submitter clinical testing

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