Submissions for variant NM_000260.4(MYO7A):c.2307del (p.Asn769fs)

dbSNP: rs1060499800

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001043738	SCV001207498	pathogenic	not provided	2021-08-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn769Lysfs*5) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of Usher syndrome (PMID: 23882135, 29490346). This variant is also known as c.2308delC. ClinVar contains an entry for this variant (Variation ID: 402264). For these reasons, this variant has been classified as Pathogenic.
King Laboratory, University of Washington	RCV001003086	SCV002059925	pathogenic	Usher syndrome type 1	2020-08-01	criteria provided, single submitter	research	MYO7A c.2307delC leads to a premature stop at codon 774. It is homozygous in 2 Palestinian children with severe to profound pre-lingual hearing loss and vestibular dysfunction (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and absent from gnomAD v2.1.1.
Hereditary Research Laboratory, Bethlehem University	RCV000454349	SCV000538102	pathogenic	Autosomal recessive nonsyndromic hearing loss 2	2016-06-04	no assertion criteria provided	research	severe to profound, GU3 vision OK but balance problems
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003086	SCV001161145	pathogenic	Usher syndrome type 1	2019-06-23	no assertion criteria provided	research