Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000779422 | SCV000916038 | uncertain significance | Renal hypomagnesemia 4 | 2018-12-06 | criteria provided, single submitter | clinical testing | The EGF c.1180C>T (p.Arg394Ter) variant is a stop-gained variant predicted to result in premature termination of the protein. The variant was observed by ICSL 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 for this variant, it 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. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive renal hypomagnesemia. |
Fulgent Genetics, |
RCV000779422 | SCV002776255 | uncertain significance | Renal hypomagnesemia 4 | 2022-03-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003396353 | SCV004121871 | uncertain significance | not specified | 2023-10-19 | criteria provided, single submitter | clinical testing | Variant summary: EGF c.1180C>T (p.Arg394X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, however current evidence is not sufficient to establish loss-of-function variants in EGF as causative of disease. The variant allele was found at a frequency of 1.6e-05 in 251340 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1180C>T in individuals affected with Hypomagnesemia 4, Renal and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |