Submissions for variant NM_000260.4(MYO7A):c.4360G>A (p.Val1454Ile) (rs397516309)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine	RCV000036141	SCV000059793	likely benign	not specified	2011-02-17	criteria provided, single submitter	clinical testing	Val1454Ile in exon 33 of MYO7A: This variant is not expected to have clinical si gnificance because computational analyses (PolyPhen2, SIFT, AlignGVGD) do not su ggest a high likelihood of impact to the protein. Of note, fruitfly has an isole ucine at this position despite high nearby amino acid conservation.
Counsyl	RCV000666151	SCV000790395	uncertain significance	Deafness, autosomal recessive 2; Usher syndrome type 1	2017-03-17	criteria provided, single submitter	clinical testing
Mendelics	RCV000988612	SCV001138391	benign	Deafness, autosomal recessive 2	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV001244369	SCV001417583	uncertain significance	not provided	2019-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces valine with isoleucine at codon 1454 of the MYO7A protein (p.Val1454Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs397516309, ExAC 0.09%). This variant has been observed in an individual affected with Usher syndrome (PMID: 26338283). ClinVar contains an entry for this variant (Variation ID: 43237). 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. 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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