Submissions for variant NM_001723.7(DST):c.3336G>C (p.Glu1112Asp)

gnomAD frequency: 0.00349  dbSNP: rs34767818

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000309512	SCV000464283	uncertain significance	Hereditary sensory and autonomic neuropathy type 6	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081982	SCV000654506	likely benign	Hereditary sensory and autonomic neuropathy type 6; Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	2025-02-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000557920	SCV001154801	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	DST: BP4, BS2
Mayo Clinic Laboratories, Mayo Clinic	RCV000557920	SCV001714782	uncertain significance	not provided	2019-10-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000557920	SCV001826024	uncertain significance	not provided	2021-06-07	criteria provided, single submitter	clinical testing	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: 25790160)
Ambry Genetics	RCV002523571	SCV003549588	uncertain significance	Inborn genetic diseases	2022-11-02	criteria provided, single submitter	clinical testing	Unlikely to be causative of DST-related sensory and autonomic neuropathy (AR) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005238941	SCV005884140	likely benign	not specified	2024-12-10	criteria provided, single submitter	clinical testing	Variant summary: DST c.3336G>C (p.Glu1112Asp) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0035 in 250036 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 3-fold of the estimated maximal expected allele frequency for a pathogenic variant in DST causing Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency phenotype (0.0011). c.3336G>C has been reported in the literature in an individual affected with progressive neuropathies, muscle weakness, Raynauds phenomenon, scleroderma syncope and hypermobility, without strong evidence for causality (Bloss_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25790160). ClinVar contains an entry for this variant (Variation ID: 357589). Based on the evidence outlined above, the variant was classified as likely benign.
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000309512	SCV004174790	uncertain significance	Hereditary sensory and autonomic neuropathy type 6	2016-01-06	no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV003972505	SCV004793595	likely benign	DST-related disorder	2020-03-12	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Molecular Biology and Genetics, Acibadem University	RCV005052809	SCV005686434	likely pathogenic	Multiple sclerosis	2024-06-10	no assertion criteria provided	research