ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6700G>A (p.Val2234Met) (rs112084407)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000245529 SCV000317882 benign Cardiovascular phenotype 2014-10-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Does not segregate with disease in family study (genes with complete penetrance)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769627 SCV000901025 benign Thoracic aortic aneurysm and aortic dissection 2016-06-02 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center RCV000029766 SCV000190200 likely benign Marfan syndrome 2016-08-15 no assertion criteria provided research Originally interpreted based on literature review PMID: 25637381. Found in patient having exome sequencing for an unrelated indication. No known history of Marfan syndrome.
Center for Human Genetics, Inc RCV000659568 SCV000781402 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000029766 SCV000807914 likely benign Marfan syndrome 2018-06-01 criteria provided, single submitter clinical testing
Color RCV000769627 SCV000903361 likely benign Thoracic aortic aneurysm and aortic dissection 2018-04-26 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726908 SCV000704103 uncertain significance not provided 2017-01-11 criteria provided, single submitter clinical testing
GeneDx RCV000035252 SCV000233880 likely benign not specified 2018-02-28 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.
Illumina Clinical Services Laboratory,Illumina RCV000273547 SCV000392196 likely benign Geleophysic dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000310000 SCV000392197 likely benign Acromicric dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000029766 SCV000392198 likely benign Marfan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000270709 SCV000392199 likely benign Ectopia lentis 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000029766 SCV000052419 benign Marfan syndrome 2015-06-12 no assertion criteria provided clinical testing
Invitae RCV000460555 SCV000557055 likely benign Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2017-12-11 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035252 SCV000058898 uncertain significance not specified 2011-07-01 criteria provided, single submitter clinical testing The 6700G>A (Val2234Met) variant has been reported in the literature in one indi vidual meeting the Ghent clinical criteria for Marfan syndrome (Tjeldhorn 2006, Rand-Hendriksen 2007). However, this individual also carried a second FBN1 varia nt (Asp1113Gly) that was found in four affected family members and who were all negative for the Val2234Met variant (Rand-Hendriksen 2007). This variant has bee n identified by our laboratory in one family; two family members that are report edly minimally affected with some clinical features of Marfan syndrome carry thi s variant. Valine (Val) at amino acid position 2234 is not completely conserved in other mammals or distantly related species (cow, dog, elephant, chicken and f rog carry an alanine; opossum carries an isoleucine; fish carries a threonine). Furthermore, this variant has been reported in dbSNP (rs112084407) with a minor allele frequency of 0.002. Collectively, these data reduce the likelihood that t his change is pathogenic. However, in the absence of additional data, we cannot conclusively determine the clinical significance of this variant at this time, t hough we lean towards a likely benign role.

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