ClinVar Miner

Submissions for variant NM_000112.4(SLC26A2):c.1011TGT[3] (p.Val341del)

dbSNP: rs121908077
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000355352 SCV000228779 pathogenic not provided 2014-10-14 criteria provided, single submitter clinical testing
GeneDx RCV000355352 SCV000329831 pathogenic not provided 2022-07-18 criteria provided, single submitter clinical testing Published functional studies demonstrate abnormal sulfate transporter activity (Superti-Furga et al. 1996; Karniski et al. 2004); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-frame deletion of one amino acid in a non-repeat region; Reported previously as c.1045_1047delGTT or p.Val340del using alternate nomenclature; This variant is associated with the following publications: (PMID: 15294877, 8528239, 20301689, 10482955, 31218223, 11448940, 9637425)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586327 SCV000695414 pathogenic Sulfate transporter-related osteochondrodysplasia 2016-07-28 criteria provided, single submitter clinical testing Variant summary: The SLC26A2 c.1020_1022delTGT (p.Val341del) variant involves the deletion of a Valine in the predicted seventh transmembrane domain of the SLC26A2 protein. One in silico tool predicts a damaging outcome for this variant. This variant was found in 17/121404 control chromosomes at a frequency of 0.00014, which does not exceed the estimated maximal expected allele frequency of a pathogenic SLC26A2 variant (0.002958). The variant has been reported in multiple affected individuals in the homozygous and compound heterozygous state, and has been shown to result in impaired ability for sulfate uptake in HEK cells (comparable to negative control cells). In these transfected cells, the protein is not detected by either immunoblot analysis or confocal immunofluorescent microscopy, suggesting that this mutation is either poorly expressed or the protein is rapidly degraded in mammalian cells (Karniski_2004). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic, and this variant is considered a common disease variant. Taken together, this variant is classified as pathogenic.
Baylor Genetics RCV001004172 SCV001162985 pathogenic Atelosteogenesis type II criteria provided, single submitter clinical testing
Invitae RCV001050109 SCV001214201 pathogenic Achondrogenesis, type IB; Atelosteogenesis type II; Multiple epiphyseal dysplasia type 4; Diastrophic dysplasia 2024-01-04 criteria provided, single submitter clinical testing This variant, c.1020_1022del, results in the deletion of 1 amino acid(s) of the SLC26A2 protein (p.Val341del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs777472333, gnomAD 0.03%). This variant has been observed in individuals with SLC26A2-related disorders (PMID: 8528239, 9637425, 10482955, 31218223). ClinVar contains an entry for this variant (Variation ID: 65558). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SLC26A2 function (PMID: 11448940). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV001810418 SCV002060333 likely pathogenic Achondrogenesis, type IB; Atelosteogenesis type II; Diastrophic dysplasia 2021-11-03 criteria provided, single submitter clinical testing NM_000112.3(SLC26A2):c.1020_1022delTGT(V341del) is an in-frame deletion classified as likely pathogenic in the context of SLC26A2-related disorders. V341del has been observed in cases with relevant disease (PMID: 9637425, 8528239, 10482955). Functional assessments of this variant are available in the literature (PMID: 11448940, 15294877). V341del has been observed in population frequency databases (gnomAD: EAS 0.03%). In summary, NM_000112.3(SLC26A2):c.1020_1022delTGT(V341del) is an in-frame deletion variant that has functional support for pathogenicity and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics RCV000023571 SCV004201734 pathogenic Achondrogenesis, type IB 2023-10-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000355352 SCV004562301 pathogenic not provided 2023-10-18 criteria provided, single submitter clinical testing The SLC26A2 c.1020_1022delTGT; p.Val341del variant (rs121908077) has been described in association with SLC26A2-related chondrodysplasias (Cai 1998, Superti-Furga 1996). It is reported as pathogenic by several laboratories in ClinVar (Variation ID: 65558) and is observed in the general population at an overall frequency of 0.01% (31/276822 alleles) in the Genome Aggregation Database. This variant deletes a single valine residue, leaving the rest of the protein product in-frame. Functional characterization of the variant protein demonstrates reduced protein expression and abnormal sulfate transporter activity (Karniski 2001, Karniski 2004, Superti-Furga 1996). Based on available information, this variant is considered pathogenic. References: Cai G et al. Mutational analysis of the DTDST gene in a fetus with achondrogenesis type 1B. Am J Med Genet. 1998 Jun 16;78(1):58-60. Karniski L et al. Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene: correlation between sulfate transport activity and chondrodysplasia phenotype. Hum Mol Genet. 2001 Jul 1;10(14):1485-90. Karniski L et al. Functional expression and cellular distribution of diastrophic dysplasia sulfate transporter (DTDST) gene mutations in HEK cells. Hum Mol Genet. 2004 Oct 1;13(19):2165-71. Superti-Furga et al. Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. Nat Genet. 1996 Jan;12(1):100-2.
OMIM RCV000023571 SCV000044862 pathogenic Achondrogenesis, type IB 1998-06-16 no assertion criteria provided literature only
GeneReviews RCV000055756 SCV000086696 not provided Diastrophic dysplasia no assertion provided literature only

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