ClinVar Miner

Submissions for variant NM_006846.4(SPINK5):c.2138A>T (p.Gln713Leu)

gnomAD frequency: 0.00001  dbSNP: rs762624618
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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 RCV001205769 SCV001377043 uncertain significance Netherton syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 713 of the SPINK5 protein (p.Gln713Leu). This variant is present in population databases (rs762624618, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. ClinVar contains an entry for this variant (Variation ID: 936869). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SPINK5 protein function. 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.
GeneDx RCV001760169 SCV001991783 uncertain significance not provided 2019-08-15 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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