ClinVar Miner

Submissions for variant NM_000128.3(F11):c.400C>T (p.Gln134Ter) (rs756908183)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169273 SCV000220575 likely pathogenic Hereditary factor XI deficiency disease 2014-08-06 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726287 SCV000343432 pathogenic not provided 2016-06-26 criteria provided, single submitter clinical testing
GeneDx RCV000726287 SCV000890351 likely pathogenic not provided 2018-11-29 criteria provided, single submitter clinical testing The Q134X variant in the F11 gene has been reported previously (as Q116X due to alternate nomenclature) in the heterozygous state in an individual with a factor XI antigen level of 43%, but who did not have spontaneous bleeding or bleeding with hemostatic challenge (Dossenbach-Glaninger et al., 2006). This variant was also identified (as Q116X due to alternate nomenclature) in an individual who had minor bleeding after surgery and a factor XI antigen level of 4%, who also harbored a second variant in F11 (Castaman et al., 2008). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q134X variant is observed in 8/126520 (0.006%) alleles from individuals of non-Finnish European background in large population cohorts, and no individuals are reported to be homozygous (Lek et al., 2016). We interpret Q134X as a likely pathogenic variant.
Fulgent Genetics,Fulgent Genetics RCV000169273 SCV000893670 likely pathogenic Hereditary factor XI deficiency disease 2018-10-31 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851775 SCV000899710 pathogenic Abnormal bleeding 2019-02-01 criteria provided, single submitter research
Illumina Clinical Services Laboratory,Illumina RCV000169273 SCV000915084 uncertain significance Hereditary factor XI deficiency disease 2018-09-06 criteria provided, single submitter clinical testing The F11 c.400C>T (p.Gln134Ter) variant, also known as p.Gln116Ter, is a stop-gained variant that is predicted to result in a premature termination of the protein. Dossenbach-Glaninger et al. (2006) identified the p.Gln134Ter variant in a heterozygous state in an Austrian probands with factor XI deficiency. The proband had approximately half the normal level of factor XI. Control data are unavailable for this variant, which is reported at a frequency of 0.000063 in the European (non-Finnish) population of the Genome Aggregation Database. Due to the potential impact of stop-gained variants and the limited evidence from the literature, the p.Gln134Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for factor XI deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Natera, Inc. RCV001273716 SCV001457098 likely pathogenic Plasma factor XI deficiency 2020-09-16 no assertion criteria provided clinical testing

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