ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.420C>A (p.Asn140Lys)

gnomAD frequency: 0.00006  dbSNP: rs560661191
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001047976 SCV001211963 uncertain significance Glycogen storage disease, type II 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 140 of the GAA protein (p.Asn140Lys). This variant is present in population databases (rs560661191, gnomAD 0.004%). This missense change has been observed in individual(s) with limb-girdle pattern muscle weakness (PMID: 29149851). ClinVar contains an entry for this variant (Variation ID: 845000). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GAA protein function. 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.
Genome-Nilou Lab RCV001047976 SCV001787056 uncertain significance Glycogen storage disease, type II 2021-07-14 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV002264159 SCV002545980 uncertain significance not provided 2022-04-01 criteria provided, single submitter clinical testing GAA: PM2, PP4, BP4
Fulgent Genetics, Fulgent Genetics RCV001047976 SCV002812286 uncertain significance Glycogen storage disease, type II 2021-08-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002264159 SCV003828505 uncertain significance not provided 2023-08-30 criteria provided, single submitter clinical testing
GeneDx RCV002264159 SCV005414905 uncertain significance not provided 2024-05-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified by whole exome sequencing in one individual from a cohort of patients with unexplained limb-girdle muscle weakness; a second variant was not described (PMID: 29149851); This variant is associated with the following publications: (PMID: 19343043, 22253258, 29149851)
Natera, Inc. RCV001047976 SCV001453585 uncertain significance Glycogen storage disease, type II 2020-09-16 no assertion criteria provided clinical testing

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