ClinVar Miner

Submissions for variant NM_000117.3(EMD):c.103G>A (p.Glu35Lys)

gnomAD frequency: 0.00001  dbSNP: rs782222974
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465491 SCV000550247 uncertain significance X-linked Emery-Dreifuss muscular dystrophy 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 35 of the EMD protein (p.Glu35Lys). This variant is present in population databases (rs794729018, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with EMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 201780). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002390469 SCV002698613 uncertain significance Cardiovascular phenotype 2021-06-26 criteria provided, single submitter clinical testing The p.E35K variant (also known as c.103G>A), located in coding exon 2 of the EMD gene, results from a G to A substitution at nucleotide position 103. The glutamic acid at codon 35 is replaced by lysine, an amino acid with similar properties. This alteration has been seen in a healthy exome cohort, but cardiovascular history was not provided (Dharmaraj T et al. Front Cell Dev Biol, 2019 Apr;7:48). Based on data from gnomAD, the A allele has an overall frequency of 0.002% (4/174087) total alleles studied, with 1 hemizygote observed. The highest observed frequency was 0.014% (4/27043) of Latino/Admixed American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003491933 SCV003833453 uncertain significance Emery-Dreifuss muscular dystrophy 1, X-linked 2021-08-02 criteria provided, single submitter clinical testing
Natera, Inc. RCV001827988 SCV002084671 uncertain significance Emery-Dreifuss muscular dystrophy 2021-03-03 no assertion criteria provided clinical testing

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