ClinVar Miner

Submissions for variant NM_001101362.2(KBTBD13):c.331G>A (p.Asp111Asn) (rs567309902)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493391 SCV000583300 uncertain significance not provided 2017-05-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KBTBD13 gene. The D111N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D111N variant is observed in 15/69584 (0.02%) in individuals undergoing testing at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D111N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, 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 RCV000300579 SCV000393280 uncertain significance Nemaline Myopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000691093 SCV000818836 uncertain significance Nemaline myopathy 6 2018-08-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 111 of the KBTBD13 protein (p.Asp111Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KBTBD13-related disease. ClinVar contains an entry for this variant (Variation ID: 316738). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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