ClinVar Miner

Submissions for variant NM_006846.4(SPINK5):c.2386C>T (p.Arg796Trp)

gnomAD frequency: 0.00002  dbSNP: rs757605120
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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 RCV001303742 SCV001492996 uncertain significance Netherton syndrome 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 796 of the SPINK5 protein (p.Arg796Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs757605120, ExAC 0.001%). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV004036287 SCV004955507 uncertain significance Inborn genetic diseases 2024-01-29 criteria provided, single submitter clinical testing The c.2386C>T (p.R796W) alteration is located in exon 25 (coding exon 25) of the SPINK5 gene. This alteration results from a C to T substitution at nucleotide position 2386, causing the arginine (R) at amino acid position 796 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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