Submissions for variant NM_000260.4(MYO7A):c.3G>A (p.Met1Ile)

gnomAD frequency: 0.00002  dbSNP: rs782787126

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668632	SCV000793266	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2017-08-08	criteria provided, single submitter	clinical testing
Invitae	RCV001203639	SCV001374813	pathogenic	not provided	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change affects the initiator methionine of the MYO7A mRNA. The next in-frame methionine is located at codon 12. This variant is present in population databases (rs782787126, gnomAD 0.01%). Disruption of the initiator codon has been observed in individuals with autosomal recessive Usher syndrome or retinitis pigmentosa (PMID: 30459346; Invitae). ClinVar contains an entry for this variant (Variation ID: 553231). This variant disrupts the p.Gly7 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30303587). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)	RCV001526681	SCV001451438	likely pathogenic	Meniere disease	2020-12-14	criteria provided, single submitter	case-control
Natera, Inc.	RCV001829848	SCV002093091	likely pathogenic	Usher syndrome type 1B	2021-02-16	no assertion criteria provided	clinical testing