Submissions for variant NM_001110556.2(FLNA):c.7267C>T (p.Pro2423Ser)

gnomAD frequency: 0.00046  dbSNP: rs200198847

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424564	SCV000250402	likely benign	not provided	2020-10-07	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000424564	SCV000511214	likely benign	not provided	2016-09-01	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083295	SCV000556035	benign	Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315600	SCV000739098	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-04-12	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659676	SCV000781519	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000197144	SCV000856324	likely benign	not specified	2017-08-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000424564	SCV000883906	likely benign	not provided	2023-09-26	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000424564	SCV001469049	likely benign	not provided	2020-12-02	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002500606	SCV002805780	likely benign	Cardiac valvular dysplasia, X-linked; FG syndrome 2; Heterotopia, periventricular, X-linked dominant; Intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linked; Melnick-Needles syndrome; Oto-palato-digital syndrome, type I; Oto-palato-digital syndrome, type II; Terminal osseous dysplasia-pigmentary defects syndrome; Frontometaphyseal dysplasia 1	2021-12-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004530158	SCV004744195	likely benign	FLNA-related disorder	2021-04-22	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000197144	SCV005076136	likely benign	not specified	2024-04-16	criteria provided, single submitter	clinical testing	Variant summary: FLNA c.7267C>T (p.Pro2423Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00043 in 181695 control chromosomes. The observed variant frequency is approximately 1400 fold of the estimated maximal expected allele frequency for a pathogenic variant in FLNA causing Periventricular Nodular Heterotopia phenotype (3.1e-07), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.7267C>T in individuals affected with Periventricular Nodular Heterotopia and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 213485). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000424564	SCV001932402	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000424564	SCV001967625	likely benign	not provided		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000197144	SCV003839544	likely benign	not specified	2022-12-14	no assertion criteria provided	clinical testing