Submissions for variant NM_001458.5(FLNC):c.7609G>A (p.Ala2537Thr)

dbSNP: rs201486752

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001671316	SCV001888516	benign	not provided	2019-11-26	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002539665	SCV002930030	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2537 of the FLNC protein (p.Ala2537Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with FLNC-related conditions. ClinVar contains an entry for this variant (Variation ID: 1260915). 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 FLNC protein function. 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.
Revvity Omics, Revvity	RCV001671316	SCV003833213	uncertain significance	not provided	2020-02-13	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001671316	SCV005269430	benign	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV001671316	SCV005330313	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	FLNC: BS1
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001671316	SCV001931350	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001724383	SCV001954973	benign	not specified		no assertion criteria provided	clinical testing