Submissions for variant NM_000138.5(FBN1):c.5776_5778del (p.Asn1926del)

gnomAD frequency: 0.00001  dbSNP: rs886038964

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001525147	SCV000319365	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2019-02-26	criteria provided, single submitter	clinical testing	The c.5776_5778delAAT variant (also known as p.N1926del) is located in coding exon 46 of the FBN1 gene. This variant results from an in-frame deletion of 3 nucleotides at positions 5776 to 5778, causing the removal of a well-conserved asparagine residue at codon 1926. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV001525147	SCV001735189	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-11-03	criteria provided, single submitter	clinical testing	This variant causes a deletion of asparagine at codon 1926 of the FBN1 protein. 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 1/251088 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	RCV001854976	SCV002189863	uncertain significance	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-09-10	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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 263883). This variant has not been reported in the literature in individuals affected with FBN1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant, c.5776_5778del, results in the deletion of 1 amino acid(s) of the FBN1 protein (p.Asn1926del), but otherwise preserves the integrity of the reading frame.
Fulgent Genetics, Fulgent Genetics	RCV002487144	SCV002776455	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	2021-11-10	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995697	SCV004814630	uncertain significance	Marfan syndrome	2023-12-13	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid of the FBN1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251088 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.
GeneDx	RCV004777643	SCV005390686	uncertain significance	not provided	2024-03-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12938084, 31506931)