Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_000260.4(MYO7A):c.3527G>A (p.Ser1176Asn)

CA242907

196099 (ClinVar)

Gene: MYO7A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 981fcdec-991d-4878-a19d-3e45b688fc3b
Approved on: 2020-05-20
Published on: 2020-05-21

HGVS expressions

NM_000260.4:c.3527G>A
NM_000260.4(MYO7A):c.3527G>A (p.Ser1176Asn)
NM_000260.3:c.3527G>A
NM_001127180.1:c.3527G>A
NM_001127180.2:c.3527G>A
NM_001369365.1:c.3494G>A
ENST00000409619.6:c.3494G>A
ENST00000409709.7:c.3527G>A
ENST00000458169.2:n.1070G>A
ENST00000458637.6:c.3527G>A
ENST00000467137.1:n.54G>A
ENST00000481328.7:n.1070G>A
NC_000011.10:g.77189367G>A
CM000673.2:g.77189367G>A
NC_000011.9:g.76900412G>A
CM000673.1:g.76900412G>A
NC_000011.8:g.76578060G>A
NG_009086.1:g.66103G>A
NG_009086.2:g.66122G>A
More

Uncertain Significance

Met criteria codes 1
BP2
Not Met criteria codes 3
PM2 PM3 PP3

Evidence Links 4

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.3527G>A (p.Ser1176Asn) variant in MYO7A was present in 0.057% (lower bound of the 95% CI of 33/42036) of African alleles in gnomAD v3 (BS1_Supporting not met). It has been observed in at least 3 individuals with Usher syndrome type 1. However, in one proband the p.Ser1176Asn variant was observed in cis with another pathogenic/likely pathogenic variant in MYO7A (BP2; PMID: 26969326). The remaining probands did not have other pathogenic or likely pathogenic variants in MYO7A identified (PM3 and PP4 not met; PMID: 27344577, 27460420, 31479088). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BP2.
Met criteria codes
BP2
Observed in cis with another pathogenic/likely pathogenic variant in MYO7A, which was in the homozygous state (PMID: 26969326).
PubMed:27344577
PubMed:26969326
PubMed:31479088
PubMed:27460420
Not Met criteria codes
PM2
Present in 0.06617% (16/24180) of African alleles in gnomAD v2.1.1. However, in v3, present in 0.07850% (33/42036) of African alleles.
PM3
Observed in at least 3 individuals with Usher syndrome type 1; however, these probands either had possible alternate mechanisms of disease or only carried another VUS with phase unknown (PMID: 27344577, 27460420, 31479088, 26969326).
PubMed:27344577
PubMed:26969326
PubMed:31479088
PubMed:27460420
PP3
REVEL score 0.638. Alamut does not predict an impact to splicing. Several animals (including 4 mammals) in the UCSC database have Cys at this site, but none have Asn.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.