ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4195G>C (p.Asp1399His) (rs373080197)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155234 SCV000204920 uncertain significance not specified 2016-10-25 criteria provided, single submitter clinical testing The p.Asp1399His variant in MYO7A has now been identified by our laboratory in t wo individuals with hearing loss, but a variant affecting the second copy of the MYO7A gene was not identified and one of them had an alternate genetic etiology to explain the hearing loss. This variant has been identified in 3/55542 Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs373080197). Computational prediction tools and conservation an alysis suggest that the p.Asp1399His variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, th e clinical significance of the p.Asp1399His variant is uncertain.
Fulgent Genetics,Fulgent Genetics RCV000765017 SCV000896201 uncertain significance Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001037020 SCV001200411 uncertain significance not provided 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 1399 of the MYO7A protein (p.Asp1399His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs373080197, ExAC 0.04%). This variant has not been reported in the literature in individuals with MYO7A-related disease. ClinVar contains an entry for this variant (Variation ID: 178486). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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