ClinVar Miner

Submissions for variant NM_001174089.2(SLC4A11):c.671G>A (p.Trp224Ter)

dbSNP: rs746532062
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002044575 SCV002107763 pathogenic not provided 2021-06-02 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This nonsense change ‚Äãhas been observed in individual(s) with congenital hereditary endothelial dystrophy (PMID: 17397048) This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp240*) in the SLC4A11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC4A11 are known to be pathogenic (PMID: 17220209, 17679935).
Neuberg Centre For Genomic Medicine, NCGM RCV004720324 SCV005329597 likely pathogenic Congenital hereditary endothelial dystrophy of cornea 2023-05-20 criteria provided, single submitter clinical testing The observed stop gain c.671G>A(p.Trp224Ter) variant in SLC4A11 gene has been submitted to the clinvar database as pathogenic. This variant has not been reported previously in individual affected with SLC4A11 associated disorders, to our knowledge. This variant is present with an allele frequency of 0.0004% in gnomAD Exomes database. The nucleotide change c.671G>A in SLC4A11 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. Another variant [c.720G>A | p.Trp240Ter] on the same residue has previously been reported as pathogenic (Ramprasad VL, et. al., 2007), suggesting it could be of clinical significance. Additional functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic.

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