Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000692071 | SCV000819878 | likely benign | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2025-01-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001766484 | SCV001999027 | uncertain significance | not provided | 2019-09-10 | criteria provided, single submitter | clinical testing | Reported in an adult patient with myofibrillar myopathy (MFM) and lower motor neuron (LMN) syndrome (Chen et al., 2019); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 571045; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31421687) |
| Ambry Genetics | RCV002360746 | SCV002662680 | uncertain significance | Cardiovascular phenotype | 2022-04-29 | criteria provided, single submitter | clinical testing | The p.V2375I variant (also known as c.7123G>A), located in coding exon 42 of the FLNC gene, results from a G to A substitution at nucleotide position 7123. The valine at codon 2375 is replaced by isoleucine, an amino acid with highly similar properties. This alteration has been reported in an individual with features of myofibrillar myopathy (Chen J et al. BMC Neurol, 2019 Aug;19:198). An alternate amino acid substitution at this codon, p.V2375F, was reported in one individual with hypertrophic cardiomyopathy; however clinical details were limited (Gómez J et al. Circ Cardiovasc Genet, 2017 Apr;10:[Epub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV001766484 | SCV003833030 | uncertain significance | not provided | 2021-11-10 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005056437 | SCV005727172 | likely benign | not specified | 2024-11-04 | criteria provided, single submitter | clinical testing | Variant summary: FLNC c.7123G>A (p.Val2375Ile) results in a conservative amino acid change located in the Filamin/ABP280 repeat profile (IPR017868) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 249434 control chromosomes. The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in FLNC causing Cardiomyopathy phenotype (1.1e-05). c.7123G>A has been reported in the literature in individuals affected with Cardiomyopathy (Chen_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31421687). ClinVar contains an entry for this variant (Variation ID: 571045). Based on the evidence outlined above, the variant was classified as likely benign. |