ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.4390G>A (p.Asp1464Asn)

gnomAD frequency: 0.00001  dbSNP: rs368396727
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815077 SCV000955520 uncertain significance RYR1-related disorder 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1464 of the RYR1 protein (p.Asp1464Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs368396727, ExAC 0.005%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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.
Ambry Genetics RCV002534859 SCV003557562 uncertain significance Inborn genetic diseases 2021-07-16 criteria provided, single submitter clinical testing The c.4390G>A (p.D1464N) alteration is located in exon 30 (coding exon 30) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 4390, causing the aspartic acid (D) at amino acid position 1464 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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