ClinVar Miner

Submissions for variant NM_005219.5(DIAPH1):c.3767C>T (p.Thr1256Ile)

gnomAD frequency: 0.00001  dbSNP: rs546064158
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000812247 SCV000952555 uncertain significance Autosomal dominant nonsyndromic hearing loss 1; Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome 2021-01-16 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1256 of the DIAPH1 protein (p.Thr1256Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs546064158, ExAC 0.006%). 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. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DIAPH1-related disease.

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