Submissions for variant NM_000138.5(FBN1):c.6440G>A (p.Gly2147Asp)

dbSNP: rs1597525958

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069529	SCV001234702	likely pathogenic	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2019-12-06	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with clinical features of Marfan syndrome (Invitae). In at least one individual the variant was observed to be de novo. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 2147 of the FBN1 protein (p.Gly2147Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150356	SCV003837668	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-06-23	criteria provided, single submitter	clinical testing
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV000859994	SCV000967796	uncertain significance	Congenital scoliosis	2019-06-12	no assertion criteria provided	research