ClinVar Miner

Submissions for variant NM_005982.4(SIX1):c.191G>A (p.Arg64His)

gnomAD frequency: 0.00003  dbSNP: rs1051653507
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000512900 SCV000608704 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
Invitae RCV000706990 SCV000836066 uncertain significance Branchiootic syndrome 3; Autosomal dominant nonsyndromic hearing loss 23 2022-09-23 criteria provided, single submitter clinical testing 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. 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 SIX1 protein function. ClinVar contains an entry for this variant (Variation ID: 444331). This variant has not been reported in the literature in individuals affected with SIX1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 64 of the SIX1 protein (p.Arg64His).
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375398 SCV001571879 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PM2_Moderate, PP3_Supporting
GeneDx RCV000512900 SCV001813522 likely benign not provided 2020-03-12 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002524959 SCV003721477 uncertain significance Inborn genetic diseases 2022-01-18 criteria provided, single submitter clinical testing The c.191G>A (p.R64H) alteration is located in exon 1 (coding exon 1) of the SIX1 gene. This alteration results from a G to A substitution at nucleotide position 191, causing the arginine (R) at amino acid position 64 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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