ClinVar Miner

Submissions for variant NM_004211.5(SLC6A5):c.1472A>G (p.Tyr491Cys)

gnomAD frequency: 0.00006  dbSNP: rs121908494
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000006119 SCV003515886 uncertain significance Hyperekplexia 3 2022-08-08 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 491 of the SLC6A5 protein (p.Tyr491Cys). This variant is present in population databases (rs121908494, gnomAD 0.003%). This missense change has been observed in individual(s) with hyperekplexia (PMID: 16751771). ClinVar contains an entry for this variant (Variation ID: 5763). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV000006119 SCV000026301 pathogenic Hyperekplexia 3 2006-07-01 no assertion criteria provided literature only
GeneReviews RCV000006119 SCV000054571 pathologic Hyperekplexia 3 2012-10-04 no assertion criteria provided curation Converted during submission to Pathogenic.

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