ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3811G>A (p.Ala1271Thr)

gnomAD frequency: 0.00001  dbSNP: rs993279983
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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 RCV001302603 SCV001491817 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-08-17 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 1005680). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1271 of the FBN1 protein (p.Ala1271Thr).
All of Us Research Program, National Institutes of Health RCV004005014 SCV004839492 uncertain significance Marfan syndrome 2023-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782699 SCV005395572 uncertain significance not specified 2024-09-09 criteria provided, single submitter clinical testing Variant summary: FBN1 c.3811G>A (p.Ala1271Thr) results in a non-conservative amino acid change located in the EGF-like domain (IPR000742) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251146 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3811G>A in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1005680). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences RCV004727106 SCV005335763 uncertain significance FBN1-related disorder 2024-04-09 no assertion criteria provided clinical testing The FBN1 c.3811G>A variant is predicted to result in the amino acid substitution p.Ala1271Thr. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. 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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