ClinVar Miner

Submissions for variant NM_001101426.4(CRPPA):c.626G>C (p.Arg209Thr)

gnomAD frequency: 0.00005  dbSNP: rs374054216
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000319984 SCV000468016 uncertain significance Congenital Muscular Dystrophy, alpha-dystroglycan related 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001053234 SCV001217484 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7; Autosomal recessive limb-girdle muscular dystrophy type 2U 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 209 of the ISPD protein (p.Arg209Thr). This variant is present in population databases (rs374054216, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ISPD-related conditions. ClinVar contains an entry for this variant (Variation ID: 359589). 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.
Revvity Omics, Revvity Omics RCV003137979 SCV003828639 uncertain significance not provided 2023-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV003372693 SCV004064493 uncertain significance Inborn genetic diseases 2023-07-12 criteria provided, single submitter clinical testing The c.626G>C (p.R209T) alteration is located in exon 3 (coding exon 3) of the ISPD gene. This alteration results from a G to C substitution at nucleotide position 626, causing the arginine (R) at amino acid position 209 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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