ClinVar Miner

Submissions for variant NM_175875.5(SIX5):c.1655C>T (p.Thr552Met)

gnomAD frequency: 0.00023  dbSNP: rs80356464
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000009132 SCV001141107 uncertain significance Branchiootorenal syndrome 2 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001851753 SCV002193122 uncertain significance not provided 2023-08-04 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 552 of the SIX5 protein (p.Thr552Met). This variant is present in population databases (rs80356464, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with branchio-oto-renal syndrome (PMID: 17357085, 24429398). ClinVar contains an entry for this variant (Variation ID: 8601). 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 SIX5 protein function. Experimental studies have shown that this missense change affects SIX5 function (PMID: 17357085). 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 RCV000009132 SCV000029349 uncertain significance Branchiootorenal syndrome 2 2011-02-01 no assertion criteria provided literature only
GeneReviews RCV000009132 SCV000041678 not provided Branchiootorenal syndrome 2 no assertion provided literature only

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