Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostics Services |
RCV003334472 | SCV004042837 | likely pathogenic | Congenital myotonia, autosomal dominant form | 2023-10-03 | criteria provided, single submitter | clinical testing | The c.869T>C variant is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or our in-house exome database. This variant has neither been reported in the literature in individuals with CLCN1-related conditions nor reported to clinical databases like ClinVar, Human Genome Mutation Database (HGMD) or OMIM in any affected individuals. In-silico pathogenicity programs like SIFT, PolyPhen-2, MutationTaster2, CADD, Varsome, Franklin etc predicted this variant to be likely deleterious however these predictions were not confirmed by published functional studies. This variant is located in a mutational hotspot region of the gene and a different amino acid change in the same codon (c.870C>G, p.Ile290Met) has been previously observed in affected individuals, published in literature several times and reported to the clinical databases as ‘Pathogenic’, by multiple submitters. |