ClinVar Miner

Submissions for variant NM_152490.5(B3GALNT2):c.727G>C (p.Val243Leu) (rs755405777)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521711 SCV000620451 uncertain significance not provided 2017-09-12 criteria provided, single submitter clinical testing The V243L variant in the B3GALNT2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V243L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We therefore interpret V243L as a variant of uncertain significance.
Invitae RCV000688969 SCV000816601 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 243 of the B3GALNT2 protein (p.Val243Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with B3GALNT2-related disease. ClinVar contains an entry for this variant (Variation ID: 451717). 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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