Submissions for variant NM_001999.4(FBN2):c.3907C>A (p.Pro1303Thr)

dbSNP: rs2126896759

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001768556	SCV001992338	uncertain significance	not provided	2019-04-19	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Although located in a calcium-binding EGF-like domain of the FBN2 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2 related disorders (Collod-Beroud et al., 2003; Frederic et al., 2009).
3billion	RCV002250768	SCV002521565	uncertain significance	Congenital contractural arachnodactyly	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.82; 3Cnet: 0.79). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.