Submissions for variant NM_000243.3(MEFV):c.608T>C (p.Leu203Pro)

gnomAD frequency: 0.00001  dbSNP: rs1959084389

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001995528	SCV002275287	uncertain significance	Familial Mediterranean fever	2021-08-13	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with proline at codon 203 of the MEFV protein (p.Leu203Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MEFV-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The proline 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002264442	SCV002542294	uncertain significance	Autoinflammatory syndrome	2020-01-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001995528	SCV003802296	uncertain significance	Familial Mediterranean fever	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126069	SCV003802297	likely benign	Familial Mediterranean fever, autosomal dominant	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003126070	SCV003802298	likely benign	Acute febrile neutrophilic dermatosis	2023-02-08	criteria provided, single submitter	clinical testing