Submissions for variant NM_001374736.1(DST):c.2504G>A (p.Arg835His)

gnomAD frequency: 0.00064  dbSNP: rs41267671

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000273786	SCV000464308	uncertain significance	Hereditary sensory and autonomic neuropathy type 6	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534052	SCV000654567	uncertain significance	Hereditary sensory and autonomic neuropathy type 6; Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	2022-11-03	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 298 of the DST protein (p.Arg298His). This variant is present in population databases (rs41267671, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DST-related conditions. ClinVar contains an entry for this variant (Variation ID: 357614). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine 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.
Ambry Genetics	RCV002446609	SCV002733692	uncertain significance	Inborn genetic diseases	2021-09-17	criteria provided, single submitter	clinical testing	The p.R802H variant (also known as c.2405G>A), located in coding exon 18 of the DST gene, results from a G to A substitution at nucleotide position 2405. The arginine at codon 802 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV003320636	SCV004025606	uncertain significance	not provided	2024-08-30	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV003320636	SCV005910007	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	DST: BP4