ClinVar Miner

Submissions for variant NM_031475.3(ESPN):c.935C>T (p.Ser312Leu)

gnomAD frequency: 0.00012  dbSNP: rs189442618
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519748 SCV000618240 uncertain significance not provided 2019-08-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 17667943, 30622556)
Fulgent Genetics, Fulgent Genetics RCV000764073 SCV000895027 uncertain significance Autosomal recessive nonsyndromic hearing loss 36 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000764073 SCV001157916 uncertain significance Autosomal recessive nonsyndromic hearing loss 36 2018-12-19 criteria provided, single submitter clinical testing The ESPN c.935C>T; p.Ser312Leu variant (rs189442618), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 449818). This variant is found in the non-Finnish European population with an overall allele frequency of 0.02% (27/121080 alleles) in the Genome Aggregation Database. The serine at codon 312 is weakly conserved, but computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. However, given the lack of clinical and functional data, the significance of the p.Ser312Leu variant is uncertain at this time.
Invitae RCV000519748 SCV004282555 uncertain significance not provided 2023-09-25 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 449818). This missense change has been observed in individual(s) with deafness (PMID: 30622556). This variant is present in population databases (rs189442618, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 312 of the ESPN protein (p.Ser312Leu).

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