ClinVar Miner

Submissions for variant NM_020451.3(SELENON):c.1469G>A (p.Trp490Ter)

gnomAD frequency: 0.00001  dbSNP: rs960468382
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535222 SCV000634401 pathogenic Eichsfeld type congenital muscular dystrophy 2023-08-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 461630). This variant has not been reported in the literature in individuals affected with SELENON-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Trp490*) in the SELENON gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SELENON are known to be pathogenic (PMID: 21131290, 21670436).
Eurofins Ntd Llc (ga) RCV000591683 SCV000708120 pathogenic not provided 2017-04-28 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000535222 SCV003761284 likely pathogenic Eichsfeld type congenital muscular dystrophy 2023-01-24 criteria provided, single submitter curation The p.Trp490Ter variant in SELENON has not been previously reported in the literature in individuals with SELENON-RM but has been identified in 0.009% (3/34522) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs960468382). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 461630) and has been interpreted as pathogenic by Invitae, Eurofins NTD (LLC), and PerkinElmer Genomics. This nonsense variant leads to a premature termination codon at position 490 which is predicted to lead to a truncated or absent protein. Loss of function of the SELENON gene is an established disease mechanism in autosomal recessive SELENON-RM. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive SELENON-RM. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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