Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001047379 | SCV001211332 | uncertain significance | Autosomal recessive distal spinal muscular atrophy 1; Charcot-Marie-Tooth disease axonal type 2S | 2021-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with tyrosine at codon 655 of the IGHMBP2 protein (p.Asn655Tyr). The asparagine residue is weakly conserved and there is a large physicochemical difference between asparagine and tyrosine. This variant is present in population databases (rs375023053, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV003160363 | SCV003885405 | uncertain significance | Inborn genetic diseases | 2023-02-07 | criteria provided, single submitter | clinical testing | The c.1963A>T (p.N655Y) alteration is located in exon 13 (coding exon 13) of the IGHMBP2 gene. This alteration results from a A to T substitution at nucleotide position 1963, causing the asparagine (N) at amino acid position 655 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |