Submissions for variant NM_000260.4(MYO7A):c.2120G>C (p.Arg707Pro)

dbSNP: rs782176754

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001089550	SCV001244761	uncertain significance	Autosomal recessive nonsyndromic hearing loss 2	2018-06-26	criteria provided, single submitter	clinical testing	A heterozygous missense variant, NM_000260.3(MYO7A):c.2120G>C, has been identified in exon 18 of 49 of the MYO7A gene. The variant is predicted to result in a major amino acid change from arginine to proline at position 707 of the protein (NP_000251.3(MYO7A):p.(Arg707Pro)). The arginine residue at this position has moderate conservation (100 vertebrates, UCSC), and is located within the Myosin head (motor) functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.0004% (1 heterozygote, 0 homozygotes). The variant has previously been described as a Variant of Unknown Siginificance (VUS; Deafness Variation Database). A different variant in the same codon resulting in a change to cysteine has also been reported as a VUS and a change to histidine has been reported as Likely Benign (Deafness Variation Database). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).