ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4075A>G (p.Ile1359Val)

gnomAD frequency: 0.00001  dbSNP: rs202192505
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002314353 SCV000738880 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-03-29 criteria provided, single submitter clinical testing The p.I1359V variant (also known as c.4075A>G), located in coding exon 32 of the FBN1 gene, results from an A to G substitution at nucleotide position 4075. The isoleucine at codon 1359 is replaced by valine, an amino acid with highly similar properties, and is located in the cbEGF-like #18 domain. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001770550 SCV001992651 uncertain significance not provided 2019-04-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1 related disorders (Collod-Beroud et al., 2003).; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 519762; Landrum et al., 2016)
Labcorp Genetics (formerly Invitae), Labcorp RCV001868124 SCV002144911 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-10-24 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477356 SCV002787752 uncertain significance Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2021-12-03 criteria provided, single submitter clinical testing

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