Submissions for variant NM_000243.3(MEFV):c.343C>A (p.Pro115Thr)

dbSNP: rs147557169

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000221844	SCV000279025	uncertain significance	not provided	2021-09-23	criteria provided, single submitter	clinical testing	Observed heterozygous in a patient with familial Mediterranean fever in published literature; however, specific patient information was not provided (Ebadi N et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28421071, 28943464)
Illumina Laboratory Services, Illumina	RCV000083246	SCV000396783	uncertain significance	Familial Mediterranean fever	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193206	SCV001361912	uncertain significance	not specified	2022-07-28	criteria provided, single submitter	clinical testing	Variant summary: MEFV c.343C>A (p.Pro115Thr) 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 0.0004 in 247544 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in MEFV causing Familial Mediterranean Fever (0.0004 vs 0.022), allowing no conclusion about variant significance. The variant, c.343C>A, has been reported in the literature in individuals affected with Familial Mediterranean Fever (example, Ebadi_2017). This report however, does not provide unequivocal conclusions about association of the variant with Familial Mediterranean Fever. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified this variant as uncertain significance (n=4) (VUS, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae	RCV000083246	SCV001640092	likely benign	Familial Mediterranean fever	2024-01-22	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262627	SCV002543757	uncertain significance	Autoinflammatory syndrome	2021-10-09	criteria provided, single submitter	clinical testing
Medical Biology Lab, Gaziantep University	RCV000083246	SCV000115320	not provided	Familial Mediterranean fever		no assertion provided	not provided
Natera, Inc.	RCV000083246	SCV001457157	uncertain significance	Familial Mediterranean fever	2020-09-16	no assertion criteria provided	clinical testing