ClinVar Miner

Submissions for variant NM_052867.4(NALCN):c.5138G>A (p.Gly1713Asp)

gnomAD frequency: 0.00001  dbSNP: rs2031085413
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV001837377 SCV002097945 uncertain significance Hypotonia, infantile, with psychomotor retardation and characteristic facies 1; Congenital contractures of the limbs and face, hypotonia, and developmental delay 2021-02-19 criteria provided, single submitter clinical testing The inherited heterozygous c.5138G>A (p.Gly1713Asp) missense variant identified in the NALCN gene has not been reported in affected individual in the literature. The variant has been reported once in the gnomAD(v3) database (1out of 152222 heterozygous alleles) suggesting it is not a common benign allele in the populations represented in that database.The variant affects an evolutionarily conserved residue and is predicted deleterious by multiple in silico tools. Functional studies to evaluate the potential consequencesof this variant have not been reported. Based on the available evidence, the inherited heterozygous c.5138G>A (p.Gly1713Asp) missense variant identified in the NALCN gene is reported as a variant of uncertain significance.
Ambry Genetics RCV002542805 SCV003625347 uncertain significance Inborn genetic diseases 2022-05-11 criteria provided, single submitter clinical testing The c.5138G>A (p.G1713D) alteration is located in exon 44 (coding exon 43) of the NALCN gene. This alteration results from a G to A substitution at nucleotide position 5138, causing the glycine (G) at amino acid position 1713 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003565504 SCV004312675 uncertain significance not provided 2023-08-07 criteria provided, single submitter clinical testing 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. 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 NALCN protein function. ClinVar contains an entry for this variant (Variation ID: 1341897). This variant has not been reported in the literature in individuals affected with NALCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1713 of the NALCN protein (p.Gly1713Asp).

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