ClinVar Miner

Submissions for variant NM_005055.5(RAPSN):c.1066G>A (p.Val356Met)

gnomAD frequency: 0.00005  dbSNP: rs570140663
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000404405 SCV000372439 uncertain significance Congenital myasthenic syndrome 11 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.
Illumina Laboratory Services, Illumina RCV000307953 SCV000372440 uncertain significance Fetal akinesia deformation sequence 1 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 RCV000706275 SCV000835315 uncertain significance Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 356 of the RAPSN protein (p.Val356Met). This variant is present in population databases (rs570140663, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAPSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 304970). 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 RAPSN 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.
Fulgent Genetics, Fulgent Genetics RCV002487360 SCV002776170 uncertain significance Congenital myasthenic syndrome 11; Fetal akinesia deformation sequence 2 2022-01-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV003243062 SCV003941465 uncertain significance Inborn genetic diseases 2023-05-23 criteria provided, single submitter clinical testing The c.1066G>A (p.V356M) alteration is located in exon 7 (coding exon 7) of the RAPSN gene. This alteration results from a G to A substitution at nucleotide position 1066, causing the valine (V) at amino acid position 356 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003488516 SCV004236550 uncertain significance not provided 2023-06-20 criteria provided, single submitter clinical testing
Natera, Inc. RCV001274400 SCV001458527 uncertain significance Congenital myasthenic syndrome 2020-04-13 no assertion criteria provided clinical testing

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