ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2735A>G (p.Asp912Gly)

gnomAD frequency: 0.00003  dbSNP: rs754919275
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001213808 SCV001385458 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-07-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002484164 SCV002794052 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 2021-11-02 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004010698 SCV004833379 uncertain significance Marfan syndrome 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 912 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Although functional studies have not been reported for this variant, it changes a conserved aspartic acid residue in the calcium-binding consensus sequence in a cbEGF-like domain and is expected to disrupt FBN1 protein function (PMID: 31227806). To our knowledge, this variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 3/250728 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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