The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: MYO7A vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000260.4(MYO7A):c.397C>A (p.His133Asn)

CA177366

164656 (ClinVar)

Gene: MYO7A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
UUID: 6fb982bb-5354-443c-9de4-3efaeacbd10c
Approved on: 2025-03-12
Published on: 2025-03-28

HGVS expressions

NM_000260.4:c.397C>A
NM_000260.4(MYO7A):c.397C>A (p.His133Asn)
NC_000011.10:g.77156018C>A
CM000673.2:g.77156018C>A
NC_000011.9:g.76867064C>A
CM000673.1:g.76867064C>A
NC_000011.8:g.76544712C>A
NG_009086.1:g.32755C>A
NG_009086.2:g.32773C>A
ENST00000409709.9:c.397C>A
ENST00000409619.6:c.364C>A
ENST00000409709.7:c.397C>A
ENST00000409893.5:c.397C>A
ENST00000458637.6:c.397C>A
ENST00000620575.4:c.397C>A
NM_000260.3:c.397C>A
NM_001127179.2:c.397C>A
NM_001127180.1:c.397C>A
NM_001127180.2:c.397C>A
NM_001369365.1:c.364C>A
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Likely Pathogenic

Met criteria codes 4
PM5 PM3 PP3 PP4
Not Met criteria codes 3
PM2 BS1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.397C>A variant in MYO7A is a missense variant predicted to cause substitution of histidine by asparagine at amino acid 133 (p.His133Asn). The filtering allele frequency in gnomAD v4 is 0.01079% (147/1179888) in the European (non-Finnish) population. (PM2_Supporting, BS1, and BA1 are not met). This variant has been reported as compound heterozygous, phase unknown, with a pathogenic variant in three individuals. One individual had a phenotype of Usher syndrome, one individual had congenital, severe to profound hearing loss, and one individual had inherited retinal disease (PM3, PP4; PMID: 36011334, 26969326, 38219857). Two additional individuals with clinical features of Usher syndrome harbored the variant phase unknown with another variant of uncertain significance (PMID: 37466950, SCV001218757.5). The computational predictor REVEL gives a score of 0.937, which is above the threshold necessary to apply PP3 (PP3). Another missense variant, c.397C>T p.His133Tyr, in the same codon has been classified as pathogenic for Usher syndrome by the ClinGen Hearing Loss VCEP (PM5; ClinVar Variation ID: 43228). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM3, PP4, PP3, PM5. (ClinGen Hearing Loss VCEP specifications version 2; 03/12/2025).
Met criteria codes
PM5
Another missense variant, c.397C>T p.His133Tyr, in the same codon has been classified as pathogenic for Usher syndrome by the ClinGen Hearing Loss VCEP
PM3
One individual had a phenotype of Usher syndrome, one individual had congenital, severe to profound hearing loss, and one individual had inherited retinal disease
PP3
The computational predictor REVEL gives a score of 0.937, which is above the threshold necessary to apply PP3
PP4
One individual had a phenotype of Usher syndrome, one individual had congenital, severe to profound hearing loss, and one individual had inherited retinal disease
Not Met criteria codes
PM2
The filtering allele frequency in gnomAD v4 is 0.01079% (147/1179888) in the European (non-Finnish) population
BS1
The filtering allele frequency in gnomAD v4 is 0.01079% (147/1179888) in the European (non-Finnish) population
BA1
The filtering allele frequency in gnomAD v4 is 0.01079% (147/1179888) in the European (non-Finnish) population
Curation History
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