ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3523A>G (p.Ile1175Val)

gnomAD frequency: 0.00003  dbSNP: rs756754760
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001301453 SCV001490622 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-09-15 criteria provided, single submitter clinical testing
GeneDx RCV001797170 SCV002038851 uncertain significance not provided 2021-06-18 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; 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); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#1004707; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27535533, 26582918, 12938084, 25652356)
Ambry Genetics RCV002451670 SCV002616028 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-07-28 criteria provided, single submitter clinical testing The p.I1175V variant (also known as c.3523A>G), located in coding exon 28 of the FBN1 gene, results from an A to G substitution at nucleotide position 3523. The isoleucine at codon 1175 is replaced by valine, an amino acid with highly similar properties. This variant was detected in a case referred for FBN1 genetic testing who did not meet Ghent criteria at the time of study, and segregation studies were inconclusive (Baudhuin LM et al. J Hum Genet, 2015 May;60:241-52). This amino acid position is not well conserved in available 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.
Fulgent Genetics, Fulgent Genetics RCV002476397 SCV002781043 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 2021-10-18 criteria provided, single submitter clinical testing

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