ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.2507C>T (p.Thr836Met)

dbSNP: rs957177447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000680530 SCV000807933 uncertain significance Connective tissue disorder 2018-06-01 criteria provided, single submitter clinical testing
Invitae RCV000685346 SCV000812824 uncertain significance Congenital contractural arachnodactyly 2023-08-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 561298). This variant has not been reported in the literature in individuals affected with FBN2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 836 of the FBN2 protein (p.Thr836Met).
GeneDx RCV003106019 SCV003761874 uncertain significance not provided 2022-07-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with Usher syndrome who also harbored a second FBN2 variant and a MYH14 variant (Bahena et al., 2022); 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: 34148116, 19006240, 18767143)

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