ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.7114G>A (p.Gly2372Ser)

dbSNP: rs2042988137
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001314686 SCV001505229 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-01-08 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 2372 of the FBN1 protein (p.Gly2372Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine.
PreventionGenetics, part of Exact Sciences RCV004727129 SCV005336464 uncertain significance FBN1-related disorder 2024-08-28 no assertion criteria provided clinical testing The FBN1 c.7114G>A variant is predicted to result in the amino acid substitution p.Gly2372Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. A different missense substitution (p.Gly2372Val) has been reported in three members of large three-generations family with thoracic aortic aneurysm and dissection (cases 1, 2 and 3 in Yamawaki et al. 2009. PubMed ID: 19336958). Two of the family members (cases 1 and 2) had an additional missense variant in TGFBR2 gene (Figure 2, Yamawaki et al. 2009. PubMed ID: 19336958). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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