ClinVar Miner

Submissions for variant NM_002180.3(IGHMBP2):c.596C>T (p.Ala199Val)

gnomAD frequency: 0.00001  dbSNP: rs780802298
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV000856963 SCV001336669 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV001320701 SCV001511497 uncertain significance Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S 2022-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 199 of the IGHMBP2 protein (p.Ala199Val). This variant is present in population databases (rs780802298, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 694854). 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 expected to disrupt IGHMBP2 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.
Ambry Genetics RCV002538887 SCV003753056 uncertain significance Inborn genetic diseases 2022-04-14 criteria provided, single submitter clinical testing The c.596C>T (p.A199V) alteration is located in exon 5 (coding exon 5) of the IGHMBP2 gene. This alteration results from a C to T substitution at nucleotide position 596, causing the alanine (A) at amino acid position 199 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genesis Genome Database RCV000856963 SCV000999528 uncertain significance Charcot-Marie-Tooth disease 2019-08-14 no assertion criteria provided research

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