Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000594000 | SCV000702665 | uncertain significance | not provided | 2016-11-15 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000083802 | SCV001139867 | uncertain significance | Familial Mediterranean fever | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000083802 | SCV001418589 | uncertain significance | Familial Mediterranean fever | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 289 of the MEFV protein (p.Ala289Val). This variant is present in population databases (rs104895132, gnomAD 0.02%). This missense change has been observed in individual(s) with MEFV-related conditions (PMID: 20041150, 25821352). ClinVar contains an entry for this variant (Variation ID: 97550). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Gene |
RCV000594000 | SCV002005213 | uncertain significance | not provided | 2023-08-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17665448, 26984802, 19790133, no PMID, 20041150, 25821352, 34426522, 35358658, 31512232) |
Genome Diagnostics Laboratory, |
RCV002262656 | SCV002542310 | uncertain significance | Autoinflammatory syndrome | 2021-04-30 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002483165 | SCV002781247 | uncertain significance | Familial Mediterranean fever; Familial Mediterranean fever, autosomal dominant; Acute febrile neutrophilic dermatosis | 2022-04-24 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114248 | SCV003800685 | uncertain significance | not specified | 2023-01-04 | criteria provided, single submitter | clinical testing | Variant summary: MEFV c.866C>T (p.Ala289Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251310 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.00012 vs 0.022), allowing no conclusion about variant significance. c.866C>T has been reported in the literature in individuals affected with Familial Mediterranean Fever, Periodic Syndrome and Stills disease who carried the variant in the heterozygous state, with no second allele reported (Feng_2009, Perko_2015, Sighart_2018, Rostmaizadeh_2019). Additionally, the variant was reported as a de novo mutation in a heterozygous patient with recurrent attacks of fever, abdominal pain, vomiting, constipation and oral aphthosis (Kosukcu_2021). 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. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genome- |
RCV000083802 | SCV003802247 | likely benign | Familial Mediterranean fever | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003126493 | SCV003802248 | benign | Familial Mediterranean fever, autosomal dominant | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003126494 | SCV003802249 | benign | Acute febrile neutrophilic dermatosis | 2023-02-08 | criteria provided, single submitter | clinical testing | |
Unité médicale des maladies autoinflammatoires, |
RCV000083802 | SCV000115901 | not provided | Familial Mediterranean fever | no assertion provided | not provided | ||
Natera, |
RCV000083802 | SCV002087428 | uncertain significance | Familial Mediterranean fever | 2020-03-30 | no assertion criteria provided | clinical testing |