Submissions for variant NM_001110556.2(FLNA):c.5873T>G (p.Met1958Arg)

dbSNP: rs587780336

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000117046	SCV000151178	uncertain significance	not provided	2013-04-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002354296	SCV002650873	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2018-11-05	criteria provided, single submitter	clinical testing	The p.M1950R variant (also known as c.5849T>G), located in coding exon 35 of the FLNA gene, results from a T to G substitution at nucleotide position 5849. The methionine at codon 1950 is replaced by arginine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, arginine is the reference amino acid in other 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002530052	SCV003487071	uncertain significance	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2022-02-19	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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLNA protein function. ClinVar contains an entry for this variant (Variation ID: 129064). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1950 of the FLNA protein (p.Met1950Arg).
CeGaT Center for Human Genetics Tuebingen	RCV000117046	SCV004165089	uncertain significance	not provided	2023-06-01	criteria provided, single submitter	clinical testing	FLNA: PM2