Variant: NM_000260.4(MYO7A):c.977T>A (p.Leu326Gln)

CA278720

164664 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 34743a4e-57ba-4093-8021-c5af895b54a0

Approved on: 2020-06-23

Published on: 2020-06-23

HGVS expressions

NM_000260.4:c.977T>A
NM_000260.4(MYO7A):c.977T>A (p.Leu326Gln)
NC_000011.10:g.77158404T>A
CM000673.2:g.77158404T>A
NC_000011.9:g.76869450T>A
CM000673.1:g.76869450T>A
NC_000011.8:g.76547098T>A
NG_009086.1:g.35141T>A
NG_009086.2:g.35159T>A
ENST00000409709.9:c.977T>A
ENST00000409619.6:c.944T>A
ENST00000409709.7:c.977T>A
ENST00000409893.5:c.977T>A
ENST00000458637.6:c.977T>A
ENST00000620575.4:c.977T>A
NM_000260.3:c.977T>A
NM_001127179.2:c.977T>A
NM_001127180.1:c.977T>A
NM_001127180.2:c.977T>A
NM_001369365.1:c.944T>A

Likely Pathogenic

• Met criteria codes: PM2 PM3 PP3 PP4

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The c.977T>A (p.Leu326Gln) variant in MYO7A was absent from gnomAD v2.1.1 (PM2).This variant has been detected in at least 2 probands with Usher syndrome. For 1 of those patients, a pathogenic or suspected-pathogenic variants was observed in trans, and in 1 the variant was observed in the homozygous state (PM3; SCV000199549.4, PMID:18181211; ClinVar ID: 164663). At least one of these probands was confirmed to have both hearing loss and retinitis pigmentosa, features highly specific for Usher syndrome (PP4). The REVEL computational prediction tool produced a score of 0.991, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PM2, PM3, PP3, PP4).

Met criteria codes

• PM2: 0.032% (1/3036) South Asian alleles in gnomAD v3 Absent from gnomAD v2.1.1
• PM3: 1.5 pts (18181211, LMM)
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline