ClinVar Miner

Submissions for variant NM_001458.5(FLNC):c.6121G>C (p.Ala2041Pro)

gnomAD frequency: 0.00002  dbSNP: rs745842738
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649100 SCV000770925 uncertain significance Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2041 of the FLNC protein (p.Ala2041Pro). This variant is present in population databases (rs745842738, gnomAD 0.002%). 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: 539372). 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. 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.
Ambry Genetics RCV002358858 SCV002655489 uncertain significance Cardiovascular phenotype 2022-10-02 criteria provided, single submitter clinical testing The p.A2041P variant (also known as c.6121G>C), located in coding exon 37 of the FLNC gene, results from a G to C substitution at nucleotide position 6121. The alanine at codon 2041 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003144437 SCV003833162 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing

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