Submissions for variant NM_170707.4(LMNA):c.1234G>T (p.Gly412Trp)

dbSNP: rs966050612

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001240466	SCV001413411	uncertain significance	Charcot-Marie-Tooth disease type 2	2020-12-26	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with tryptophan at codon 412 of the LMNA protein (p.Gly412Trp). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and tryptophan.
Ambry Genetics	RCV002375271	SCV002668052	uncertain significance	Cardiovascular phenotype	2020-10-01	criteria provided, single submitter	clinical testing	The p.G412W variant (also known as c.1234G>T), located in coding exon 7 of the LMNA gene, results from a G to T substitution at nucleotide position 1234. The glycine at codon 412 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002491793	SCV002777141	uncertain significance	Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome; Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Heart-hand syndrome, Slovenian type; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive; Restrictive dermopathy 2	2021-07-19	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528956	SCV001741600	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528956	SCV001966926	uncertain significance	not provided		no assertion criteria provided	clinical testing