ClinVar Miner

Submissions for variant NM_004211.5(SLC6A5):c.1274C>T (p.Thr425Met)

gnomAD frequency: 0.00009  dbSNP: rs121908498
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000006123 SCV002222019 uncertain significance Hyperekplexia 3 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 425 of the SLC6A5 protein (p.Thr425Met). This variant is present in population databases (rs121908498, gnomAD 0.06%). This missense change has been observed in individual(s) with hyperekplexia (PMID: 16751771). ClinVar contains an entry for this variant (Variation ID: 5767). 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 SLC6A5 protein function. Experimental studies have shown that this missense change affects SLC6A5 function (PMID: 16751771). 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.
OMIM RCV000006123 SCV000026305 pathogenic Hyperekplexia 3 2006-07-01 no assertion criteria provided literature only
GeneReviews RCV000006123 SCV000054568 not provided Hyperekplexia 3 no assertion provided literature only

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