ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.3205G>A (p.Asp1069Asn) (rs373150395)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000438769 SCV000332139 uncertain significance not provided 2015-06-11 criteria provided, single submitter clinical testing
GeneDx RCV000438769 SCV000524480 pathogenic not provided 2021-08-20 criteria provided, single submitter clinical testing Functional studies indicate that D1069N results in impaired channel function as sodium currents were reduced and the voltage dependence of the channel activation was shifted in the depolarizing direction (Zaharieva et al., 2016); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26700687, 17442264)
Invitae RCV001058903 SCV001223501 uncertain significance Familial hyperkalemic periodic paralysis 2019-03-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1069 of the SCN4A protein (p.Asp1069Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs373150395, ExAC 0.003%). This variant has been observed to segregate with autosomal recessive congenital myopathy in a family (PMID: 26700687). ClinVar contains an entry for this variant (Variation ID: 281372). This variant has been reported to have conflicting or insufficient data regarding its effect on SCN4A protein function (PMID: 26700687, 24778431). 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.