ClinVar Miner

Submissions for variant NM_003126.4(SPTA1):c.5081G>A (p.Arg1694His)

gnomAD frequency: 0.00018  dbSNP: rs201822255
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426517 SCV000536521 uncertain significance not provided 2017-01-20 criteria provided, single submitter clinical testing The R1694H variant in the SPTA1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1694H variant was not observed at any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R1694H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R1694H as a variant of uncertain significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000426517 SCV002050007 uncertain significance not provided 2021-03-23 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003388582 SCV004100417 uncertain significance Elliptocytosis 2 criteria provided, single submitter clinical testing The missense variant p.R1694H in SPTA1 (NM_003126.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge.The missense variant c.5081G>A (p.R1694H) in SPTA1 (NM_003126.4) is observed in 13/34442 (0.0377%) alleles from individuals of Latino background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. The p.R1694H missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 1694 of SPTA1 is conserved in all mammalian species. The nucleotide c.5081 in SPTA1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000426517 SCV004467743 benign not provided 2023-02-14 criteria provided, single submitter clinical testing

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