Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002860304 | SCV003632333 | uncertain significance | Inborn genetic diseases | 2022-06-24 | criteria provided, single submitter | clinical testing | The c.6004A>G (p.K2002E) alteration is located in exon 48 (coding exon 48) of the SMCHD1 gene. This alteration results from a A to G substitution at nucleotide position 6004, causing the lysine (K) at amino acid position 2002 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003649416 | SCV004374487 | uncertain significance | Facioscapulohumeral muscular dystrophy 2 | 2024-02-08 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 2002 of the SMCHD1 protein (p.Lys2002Glu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SMCHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2297107). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |