ClinVar Miner

Submissions for variant NM_001101426.4(CRPPA):c.1218T>G (p.Ile406Met)

gnomAD frequency: 0.00068  dbSNP: rs202011820
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000729934 SCV000582233 uncertain significance not provided 2016-12-08 criteria provided, single submitter clinical testing The I406M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I406M variant is observed in 14/9632 (0.15%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server)]. This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Eurofins Ntd Llc (ga) RCV000729934 SCV000857636 uncertain significance not provided 2018-06-11 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000729934 SCV001144250 uncertain significance not provided 2018-12-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001208625 SCV001380024 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 406 of the ISPD protein (p.Ile406Met). This variant is present in population databases (rs202011820, gnomAD 0.2%). This missense change has been observed in individual(s) with muscular dystrophy (PMID: 29382405). ClinVar contains an entry for this variant (Variation ID: 429621). 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: "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.
Revvity Omics, Revvity RCV000729934 SCV003828648 uncertain significance not provided 2020-01-30 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000729934 SCV004228196 uncertain significance not provided 2022-09-02 criteria provided, single submitter clinical testing

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