Submissions for variant NM_005120.3(MED12):c.3883C>T (p.Arg1295Cys)

dbSNP: rs863223706

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196935	SCV000250611	uncertain significance	not provided	2019-01-02	criteria provided, single submitter	clinical testing	The R1295C variant has not been previously reported in two brothers with MED12-related disorders and in two unaffected obligate carrier females (Charzewska et al., 2018; Hu et al., 2016). The R1295C variant is not observed in large population cohorts (Lek et al., 2016). The R1295C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in individuals with MED12-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Institute of Human Genetics, University of Leipzig Medical Center	RCV002255134	SCV002526691	likely pathogenic	X-linked intellectual disability with marfanoid habitus	2022-05-11	criteria provided, single submitter	clinical testing	This variant was identified as hemizygous._x000D_ Criteria applied: PS4_MOD, PM5, PM2_SUP, PP3
Duke University Health System Sequencing Clinic, Duke University Health System	RCV001580315	SCV003918943	pathogenic	FG syndrome 1	2023-04-20	criteria provided, single submitter	research
GeneReviews	RCV001580315	SCV001809991	not provided	FG syndrome 1		no assertion provided	literature only	Reported in a family with nonspecific intellectual disability