Submissions for variant NM_000243.3(MEFV):c.378G>T (p.Gly126=)

dbSNP: rs777867857

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001264477	SCV001442651	uncertain significance	not specified	2020-10-22	criteria provided, single submitter	clinical testing	Variant summary: MEFV c.378G>T results in a synonymous change. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 246214 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.378G>T in individuals affected with Familial Mediterranean Fever and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS - possibly benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001339993	SCV001533781	uncertain significance	Familial Mediterranean fever	2022-03-14	criteria provided, single submitter	clinical testing	This sequence change affects codon 126 of the MEFV mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MEFV protein. This variant is present in population databases (rs777867857, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MEFV-related conditions. ClinVar contains an entry for this variant (Variation ID: 984473). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Genome-Nilou Lab	RCV001339993	SCV003802403	uncertain significance	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003127740	SCV003802404	likely benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003127741	SCV003802405	likely benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001339993	SCV002087466	uncertain significance	Familial Mediterranean fever	2020-04-15	no assertion criteria provided	clinical testing