ClinVar Miner

Submissions for variant NM_007074.4(CORO1A):c.1237G>A (p.Gly413Arg)

gnomAD frequency: 0.00004  dbSNP: rs751313483
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001225523 SCV001397806 uncertain significance Severe combined immunodeficiency due to CORO1A deficiency 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 413 of the CORO1A protein (p.Gly413Arg). This variant is present in population databases (rs751313483, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CORO1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 953260). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CORO1A protein function with a negative predictive value of 80%. 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 RCV001225523 SCV003829915 uncertain significance Severe combined immunodeficiency due to CORO1A deficiency 2021-06-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV003259173 SCV003972815 uncertain significance Inborn genetic diseases 2023-05-24 criteria provided, single submitter clinical testing The c.1237G>A (p.G413R) alteration is located in exon 10 (coding exon 9) of the CORO1A gene. This alteration results from a G to A substitution at nucleotide position 1237, causing the glycine (G) at amino acid position 413 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479297 SCV004223753 uncertain significance not specified 2023-11-13 criteria provided, single submitter clinical testing Variant summary: CORO1A c.1237G>A (p.Gly413Arg) results in a non-conservative amino acid change located in the Trimerisation motif (IPR015049) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 243088 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in CORO1A causing Severe Combined Immunodeficiency (4.5e-05 vs 0.00035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1237G>A in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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