Submissions for variant NM_000138.5(FBN1):c.7181G>A (p.Arg2394Gln)

gnomAD frequency: 0.00001  dbSNP: rs199750146

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001180238	SCV001345117	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-09-21	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 2394 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251064 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.
Fulgent Genetics, Fulgent Genetics	RCV002480606	SCV002788607	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	2021-10-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235486	SCV003934307	uncertain significance	not specified	2024-04-15	criteria provided, single submitter	clinical testing	Variant summary: FBN1 c.7181G>A (p.Arg2394Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251064 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.7181G>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: 921089). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV003393867	SCV004129799	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	FBN1: PP2, BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV003769963	SCV004603498	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-02-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004006641	SCV004822401	uncertain significance	Marfan syndrome	2023-03-28	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 2394 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251064 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.