ClinVar Miner

Submissions for variant NM_001101426.4(CRPPA):c.895G>C (p.Gly299Arg) (rs373890080)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413556 SCV000492311 uncertain significance not specified 2016-12-08 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ISPD gene. The G299R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G299R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G299R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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.
Invitae RCV000819341 SCV000959995 uncertain significance Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, type A7; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 7 2019-02-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 299 of the ISPD protein (p.Gly299Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs373890080, ExAC 0.008%). This variant has not been reported in the literature in individuals with ISPD-related disease. ClinVar contains an entry for this variant (Variation ID: 373694). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000998769 SCV001155041 uncertain significance not provided 2018-08-01 criteria provided, single submitter clinical testing

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