ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5063T>C (p.Met1688Thr)

gnomAD frequency: 0.00001  dbSNP: rs771444877
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
AiLife Diagnostics, AiLife Diagnostics RCV002224388 SCV002503011 uncertain significance not provided 2021-11-18 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003528357 SCV004357370 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-07-06 criteria provided, single submitter clinical testing This missense variant replaces methionine with threonine at codon 1688 of the FBN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 3/279638 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV005213621 SCV005861164 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-12-16 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1688 of the FBN1 protein (p.Met1688Thr). This variant is present in population databases (rs771444877, gnomAD 0.002%). This missense change has been observed in individual(s) with 27906200 (FBN1-related conditions). ClinVar contains an entry for this variant (Variation ID: 1677646). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

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