Submissions for variant NM_000260.4(MYO7A):c.6231dup (p.Lys2078fs)

dbSNP: rs730880367

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000156543	SCV000206262	pathogenic	Rare genetic deafness	2014-07-22	criteria provided, single submitter	clinical testing	The p.Lys2078fs variant in MYO7A has been previously reported in one individual with hearing loss. It has not been identified in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino aci d sequence beginning at position 2078 and lead to a premature termination codon 50 amino acids downstream. This alteration is then predicted to lead to a trunca ted or absent protein. Truncating or loss of function variants in the MYO7A gen e are an established disease mechanism for Usher syndrome. In summary, this var iant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner (http://personalizedmedicine.partners.org/Laboratory- For-Molecular-Medicine/).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001850162	SCV002240322	pathogenic	not provided	2022-08-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 179745). This premature translational stop signal has been observed in individual(s) with autosomal recessive MYO7A-related conditions (PMID: 28944237, 29048421). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys2078Glufs*50) 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).
Institute of Human Genetics, University of Leipzig Medical Center	RCV003326124	SCV004032259	pathogenic	Usher syndrome type 1	2023-08-24	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PM2_SUP,PM3
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001850162	SCV005196759	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing