ClinVar Miner

Submissions for variant NM_021971.4(GMPPB):c.458C>T (p.Thr153Ile) (rs202013297)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Belal Azab Laboratory,The University of Jordan RCV000993849 SCV000930013 pathogenic Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 14 2019-07-01 criteria provided, single submitter research
Invitae RCV000815814 SCV000956286 likely pathogenic Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 14; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type b, 14; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 14 2019-08-16 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 153 of the GMPPB protein (p.Thr153Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs202013297, ExAC 0.009%). This variant has been observed to be homozygous or in combination with another GMPPB variant in several individuals affected with GMPPB-related conditions (PMID: 25681410, 28914264, 30257713). This variant has also been observed to segregate with disease in a family (Invitae). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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