Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000007626 | SCV000074679 | benign | Cystic fibrosis | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Soonchunhyang University Bucheon Hospital, |
RCV000007626 | SCV000267253 | likely benign | Cystic fibrosis | 2016-03-18 | criteria provided, single submitter | reference population | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586236 | SCV000601079 | likely benign | not provided | 2018-08-06 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000506704 | SCV000603046 | benign | not specified | 2018-10-12 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000586236 | SCV000696917 | benign | not provided | 2017-07-19 | criteria provided, single submitter | clinical testing | Variant summary: The CFTR c.2735C>T (p.Ser912Leu) variant involves the alteration of a not conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 279/304800 control chromosomes, predominantly observed in the Ashkenazi Jewish subpopulation in gnomAD at a frequency of 0.017041 (173/10152). This frequency is about 1.3 times the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603), suggesting this is likely a benign polymorphism found primarily in the populations of Ashkenazi Jewish origin. However, it needs to be noted that this observation needs to take into account the nature of this population having lower genetic heterogeneity. This variant has been reported in multiple affected individuals; however, many of the reported cases also carried p.G1244V in cis or in cis with another potentially pathogenic variant. Functional data shows that the variant of interest, alone, acts comparable to wild type function, however, in cis with another potentially pathogenic variant such as G1244V (shown to have pathogenic properties, in isolation) drastically affects functionality (Clain_2005). In addition, an asymptomatic male was compound heterozygous (in trans) for this variant and a pathogenic (p.R709X) was reported (Clain_2005), supporting for benign outcome. Furthermore, multiple clinical diagnostic laboratories/reputable databases and publications (Clain_2005 and Zietkiewicz_2014) cite the variant of interest in isolation as Benign. Therefore, taken all together, variant of interest in isolation is classified as benign, however, one must take into consideration when the variant of interest is in a complex allele with another potentially pathogenic CFTR variant (in cis), the variant of interest may act as a modifier of pathogenicity. |
EGL Genetic Diagnostics, |
RCV000586236 | SCV000700547 | uncertain significance | not provided | 2018-07-05 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000506704 | SCV000730528 | likely benign | not specified | 2018-01-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Johns Hopkins Genomics, |
RCV000007626 | SCV000886880 | benign | Cystic fibrosis | 2019-01-31 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000007626 | SCV001137486 | benign | Cystic fibrosis | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001016438 | SCV001177395 | likely benign | Inborn genetic diseases | 2018-07-05 | criteria provided, single submitter | clinical testing | In silico models in agreement (benign) ;Other data supporting benign classification |
Illumina Clinical Services Laboratory, |
RCV001158768 | SCV001320423 | uncertain significance | CFTR-related disorders | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
OMIM | RCV000007626 | SCV000027827 | benign | Cystic fibrosis | 2005-05-01 | no assertion criteria provided | literature only | |
Natera, |
RCV000007626 | SCV001455994 | benign | Cystic fibrosis | 2019-08-05 | no assertion criteria provided | clinical testing |