Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000878205 | SCV001021069 | likely benign | Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002354708 | SCV002652215 | likely benign | Cardiovascular phenotype | 2022-04-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
| Revvity Omics, |
RCV003145224 | SCV003831458 | uncertain significance | not provided | 2019-06-25 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003489954 | SCV004241798 | likely benign | not specified | 2023-12-04 | criteria provided, single submitter | clinical testing | Variant summary: FLNC c.5944C>T (p.Arg1982Cys) results in a non-conservative amino acid change in 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 0.00018 in 248716 control chromosomes, predominantly at a frequency of 0.001 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 128 fold of the estimated maximal expected allele frequency for a pathogenic variant in FLNC causing Dilated Cardiomyopathy phenotype (7.8e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.5944C>T has been reported in the literature in at-least one individual with a family history for dilated cardiomyopathy (example: Mori_2022). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 35463915). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=1) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. |