ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.6002G>A (p.Arg2001Gln)

gnomAD frequency: 0.00002  dbSNP: rs1483960506
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000996065 SCV001150526 uncertain significance not provided 2016-06-01 criteria provided, single submitter clinical testing
Invitae RCV001205098 SCV001376334 benign Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2022-07-18 criteria provided, single submitter clinical testing
GeneDx RCV000996065 SCV002569574 uncertain significance not provided 2022-03-02 criteria provided, single submitter clinical testing Reported in a fetus with tetralogy of fallot and shown to be maternally inherited (reported as c.6002 G>A; p.(R2001Q)) (Li et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32410215)
Ambry Genetics RCV002354903 SCV002656523 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-08-03 criteria provided, single submitter clinical testing The p.R1993Q variant (also known as c.5978G>A), located in coding exon 35 of the FLNA gene, results from a G to A substitution at nucleotide position 5978. The arginine at codon 1993 is replaced by glutamine, an amino acid with highly similar properties. This variant (referred to as c.6002G>A, p.Arg2001Gln) has been detected in a prenatal case with tetralogy of Fallot (Li R et al. Clin Genet. 2020 09;98(3):215-230). Based on data from gnomAD, the A allele has an overall frequency of 0.0016% (3/181587) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.007% (1/13549) of East Asian alleles. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000996065 SCV003800573 uncertain significance not provided 2022-03-18 criteria provided, single submitter clinical testing The FLNA c.5978G>A; p.Arg1993Gln variant (rs1483960506), also known as c.6002G>A; p.Arg2001Gln in transcript NM_001110556, is reported in the literature in a hemizygous fetus affected with tetralogy of Fallot (Li 2020). This variant is found on only three chromosomes (3/181587 alleles) in the Genome Aggregation Database. The arginine at codon 1993 is highly conserved, but computational analyses predict that this variant is neutral (REVEL: 0.131). Due to limited information, the clinical significance of the p.Arg1993Gln variant is uncertain at this time. References: Li R et al. Prenatal exome sequencing in fetuses with congenital heart defects. Clin Genet. 2020 Sep;98(3):215-230. PMID: 32410215.

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