ClinVar Miner

Submissions for variant NM_001101362.2(KBTBD13):c.209C>T (p.Pro70Leu) (rs766269932)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522134 SCV000620105 uncertain significance not provided 2017-08-21 criteria provided, single submitter clinical testing The P70L variant in the KBTBD13 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, this variant has been detected in 1/78584 (0.0015) alleles in presumably healthy individuals tested at GeneDx. The P70L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved, however, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P70L as a variant of uncertain significance.
Invitae RCV000701750 SCV000830565 uncertain significance Nemaline myopathy 6 2018-02-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 70 of the KBTBD13 protein (p.Pro70Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. 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: 451407). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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