ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.3557C>T (p.Ala1186Val)

dbSNP: rs1114167361
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute Of Molecular Biology And Genetics, Federal Almazov National Medical Research Centre RCV000492004 SCV000537201 likely pathogenic Hypertrophic cardiomyopathy 26 criteria provided, single submitter research The patient was diagnosed with restrictive cardiomyopathy at the age of 3 diagnosed due to atrial enlargement. Mild signs of myopathy and neuropathy including muscle hypotonia were observed and confirmed by electromyography. The parents refused the genetic screening, and so de novo character of mutation was not confirmed. Similar variant was detected in another patient with restrictive cardiomyopathy at the age of 1.5 yr. From the age of a year patient's mother was worried about hyperhidrosis, tiredness and heavy breathing. There were noted atrium dilation and open foramen ovale. Besides, myocardial contractility is without changes with an additional systolic impulse. He presented with more prominent clinical signs of myopathy and involvement of central nervous system.
Invitae RCV000538844 SCV000650989 pathogenic Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2022-10-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FLNC protein function. ClinVar contains an entry for this variant (Variation ID: 427928). This missense change has been observed in individual(s) with congenital myopathy and/or myofibrillar myopathy (PMID: 21520333, 26436962; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1186 of the FLNC protein (p.Ala1186Val).
Fulgent Genetics, Fulgent Genetics RCV000763162 SCV000893749 pathogenic Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000987973 SCV001137508 pathogenic Myofibrillar myopathy 5 2019-05-28 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000492004 SCV001368892 likely pathogenic Hypertrophic cardiomyopathy 26 2019-03-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3.
Ambry Genetics RCV001266689 SCV001444866 pathogenic Inborn genetic diseases 2019-09-18 criteria provided, single submitter clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center RCV001814165 SCV001755423 pathogenic Abnormality of the musculature 2021-07-10 criteria provided, single submitter clinical testing
GeneDx RCV001556592 SCV001778203 pathogenic not provided 2020-11-12 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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: 29858533, 32112656, 33060286, 21520333, 32154132, 26436962)
Revvity Omics, Revvity RCV001556592 SCV002023735 pathogenic not provided 2019-08-08 criteria provided, single submitter clinical testing

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