ClinVar Miner

Submissions for variant NM_024921.4(POF1B):c.986G>A (p.Arg329Gln) (rs75398746)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626964 SCV000747667 uncertain significance Premature ovarian insufficiency 2017-01-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000011541 SCV000915304 likely pathogenic Premature ovarian failure 2b 2018-03-26 criteria provided, single submitter clinical testing Lacombe et al. (2006) identified the POF1B c.986G>A (p.Arg329Gln) variant in a homozygous state in five sisters with POF from a consanguineous Lebanese family. The variant was also identified in a heterozygous state in the unaffected mother and an unaffected sister. The p.Arg329Gln variant has also been reported in two additional patients with POF, including in a heterozygous state in one patient with a second unidentified variant and in one patient with the p.Arg329Gln variant on one allele and a balanced translocation on the other (Bione et al. 2004; Ledig et al. 2015). The p.Arg329Gln variant was found in a heterozygous state in a total of seven of 992 controls from the above studies, and is reported at a frequency of 0.007634 in the admixed American population of the 1000 Genomes Project. Lacombe et al. (2006) found that in vitro binding to non-muscle actin filaments was diminished four-fold in the p.Arg329Gln variant protein compared to the wild type, and Padovano et al. (2011) demonstrated that cells expressing the p.Arg329Gln variant have mislocalized and misassembled tight junctions, were dysmorphic with altered monolayer organization, and showed defects in ciliogenesis and cystogenesis. Based on the evidence, the p.Arg329Gln variant is classified as as a variant of unknown significance but suspicious for pathogenicity for premature ovarian failure 2B. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000953408 SCV001099981 benign not provided 2018-06-15 criteria provided, single submitter clinical testing
OMIM RCV000011541 SCV000031773 pathogenic Premature ovarian failure 2b 2006-07-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.