Submissions for variant NM_000140.5(FECH):c.362A>G (p.Glu121Gly)

gnomAD frequency: 0.00043  dbSNP: rs141813907

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000391250	SCV000409669	likely benign	Protoporphyria, erythropoietic, 1	2016-06-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455865	SCV000539171	uncertain significance	not specified	2016-06-02	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: literature non available
Invitae	RCV001859931	SCV002131560	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002252096	SCV002523844	uncertain significance	See cases	2020-11-13	criteria provided, single submitter	clinical testing	ACMG classification criteria: PP3, BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000455865	SCV002547854	uncertain significance	not specified	2022-05-23	criteria provided, single submitter	clinical testing	Variant summary: FECH c.362A>G (p.Glu121Gly) results in a non-conservative amino acid change located in the Ferrochelatase, N-terminal domain (IPR033659) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00043 in 251474 control chromosomes in the gnomAD database, including 1 homozygote. This frequency does not allow conclusions about variant significance. c.362A>G has been reported in the literature in individuals affected with Protoporphyria, Erythropoietic, 1 (example, Balwani_2013, non-primary report). These report(s) do not provide unequivocal conclusions about association of the variant with Protoporphyria, Erythropoietic, 1. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=2; Likely Benign, n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.