ClinVar Miner

Submissions for variant NM_005198.5(CHKB):c.565_568del (p.Phe189fs)

dbSNP: rs752436924
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779377 SCV000915980 uncertain significance Megaconial type congenital muscular dystrophy 2017-08-30 criteria provided, single submitter clinical testing The CHKB c.565_568delTTTG (p.Phe189GlyfsTer7) variant is a frameshift variant that is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.00002 in the European (non-Finnish) population from the Genome Aggregation Database but this is based on two alleles in a region of good sequencing coverage so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital muscular dystrophy, CHKB-related. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV000779377 SCV002227891 pathogenic Megaconial type congenital muscular dystrophy 2024-06-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe189Glyfs*7) in the CHKB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHKB are known to be pathogenic (PMID: 21665002). This variant is present in population databases (rs752436924, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of congenital muscular dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 632393). For these reasons, this variant has been classified as Pathogenic.

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