ClinVar Miner

Submissions for variant NM_001101362.2(KBTBD13):c.2T>G (p.Met1Arg) (rs374196960)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579334 SCV000680641 uncertain significance not specified 2015-08-05 criteria provided, single submitter clinical testing A variant of unknown significance has been identified in the KBTBD13 gene. The c.2 T>G nucleotide substitution has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. This substitution alters the initiator Methionine codon, and the resultant protein would be described as p.Met1?" to signify that it is not known if the loss of Met1 means that all protein translation is completely prevented or if a protein is produced using an alternative Methionine initiator codon. The c.2 T>G variant was not observed with any significant frequency in approximately 5,700 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant."
Illumina Clinical Services Laboratory,Illumina RCV000542199 SCV000915691 uncertain significance Nemaline myopathy 6 2017-04-27 criteria provided, single submitter clinical testing The KBTBD13 p.Met1Arg variant is predicted to disrupt the initiation codon, and may interfere with protein expression. A literature search was performed for the gene and cDNA change. No publications were found based on this search. 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 start lost variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000542199 SCV000638786 uncertain significance Nemaline myopathy 6 2018-04-20 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the KBTBD13 mRNA. The next in-frame methionine is located at codon 40. While this variant is present in population databases (rs374196960), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This particular variant has not been reported in the literature in individuals with a KBTBD13-related disease. In addition, only missense variants in KBTBD13 have been reported to cause disease (PMID: 21109227). ClinVar contains an entry for this variant (Variation ID: 464353). In summary, this variant is a rare initiator codon change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance.

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