ClinVar Miner

Submissions for variant NM_015295.3(SMCHD1):c.1906G>A (p.Asp636Asn)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004966719 SCV005507541 uncertain significance Inborn genetic diseases 2024-10-21 criteria provided, single submitter clinical testing The c.1906G>A (p.D636N) alteration is located in exon 14 (coding exon 14) of the SMCHD1 gene. This alteration results from a G to A substitution at nucleotide position 1906, causing the aspartic acid (D) at amino acid position 636 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005107891 SCV005827500 uncertain significance Facioscapulohumeral muscular dystrophy 2 2024-07-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 636 of the SMCHD1 protein (p.Asp636Asn). This variant is present in population databases (rs776263440, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SMCHD1-related conditions. 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 SMCHD1 protein function with a negative predictive value of 80%. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.