ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3839C>T (p.Ser1280Leu)

gnomAD frequency: 0.00007  dbSNP: rs200481467
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000513271 SCV000250286 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; At the protein level, in silico analysis supports that this missense variant has a deleterious effect on protein structure/function; At the mRNA level, in silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not substitute or introduce a cysteine residue (Callewaert et al., 2009; Frederic et al., 2009); This variant is associated with the following publications: (PMID: 19006240, 18767143)
Invitae RCV000472155 SCV000553192 likely benign Congenital contractural arachnodactyly 2024-01-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000513271 SCV000609174 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002315591 SCV000739037 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-05-19 criteria provided, single submitter clinical testing The p.S1280L variant (also known as c.3839C>T), located in coding exon 29 of the FBN2 gene, results from a C to T substitution at nucleotide position 3839. The serine at codon 1280 is replaced by leucine, an amino acid with dissimilar properties, and is located in the cbEGF-like #17 domain. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277534 SCV002566574 uncertain significance Connective tissue disorder 2020-03-01 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000513271 SCV000840353 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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