Submissions for variant NM_020451.3(SELENON):c.1654G>A (p.Glu552Lys)

gnomAD frequency: 0.00036  dbSNP: rs200128474

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723596	SCV000113949	uncertain significance	not provided	2013-06-18	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000723596	SCV000615145	uncertain significance	not provided	2019-12-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000542565	SCV000634407	benign	Eichsfeld type congenital muscular dystrophy	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000723596	SCV000729489	likely benign	not provided	2021-04-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20623375)
Illumina Laboratory Services, Illumina	RCV001097379	SCV001253657	uncertain significance	SEPN1-related disorder	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV000723596	SCV001500351	uncertain significance	not provided	2022-04-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001329142	SCV001520478	uncertain significance	Congenital myopathy with fiber type disproportion	2019-12-13	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic	RCV000723596	SCV002541941	uncertain significance	not provided	2021-11-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003398681	SCV004122969	uncertain significance	not specified	2023-10-16	criteria provided, single submitter	clinical testing	Variant summary: SELENON c.1654G>A (p.Glu552Lys) results in a conservative amino acid change in 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 0.00038 in 249566 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SELENON causing Eichsfeld Type Congenital Muscular Dystrophy (0.00038 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1654G>A in individuals affected with Eichsfeld Type Congenital Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=2) and benign/likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV000542565	SCV004237870	likely benign	Eichsfeld type congenital muscular dystrophy	2022-05-23	criteria provided, single submitter	clinical testing