Submissions for variant NM_001110556.2(FLNA):c.1621G>A (p.Glu541Lys)

gnomAD frequency: 0.00004  dbSNP: rs743546

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000200807	SCV000250441	likely benign	not provided	2020-12-31	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002315603	SCV000739070	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-12-18	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae	RCV002228873	SCV000824365	likely benign	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2023-11-03	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV001804931	SCV002051782	likely benign	Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked	2021-11-16	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000200807	SCV002541776	uncertain significance	not provided	2021-04-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003417707	SCV004117220	uncertain significance	FLNA-related condition	2022-09-07	criteria provided, single submitter	clinical testing	The FLNA c.1621G>A variant is predicted to result in the amino acid substitution p.Glu541Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD, including four hemizygous individuals (http://gnomad.broadinstitute.org/variant/X-153593574-C-T). Although we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.