ClinVar Miner

Submissions for variant NM_001101426.4(CRPPA):c.614G>A (p.Arg205His)

gnomAD frequency: 0.00003  dbSNP: rs566179705
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000706667 SCV000835732 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U 2021-09-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 205 of the ISPD protein (p.Arg205His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with Walker-Warburg syndrome (PMID: 24120487). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. 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 disruptive. 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.
GeneDx RCV001592911 SCV001814553 likely pathogenic not provided 2021-06-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 26687144, 24120487)

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