The TECTA mutation R1890C is identified as one of the causes of genetic hearing loss: a case report

BMC Medical Genetics

Table 2 Pathogenicity evaluation of two variants based on in-depth ACMG guideline application

Gene	Variant	Literature reported the variant				In-depth ACMG guideline interpretation
Gene	Variant	Literature 1		Literature 2		Original ACMG guideline application			Hearing loss-specified ACMG guideline application^a
		PMID (year)	Evidential level	PMID (year)	Evidential level	Pathogenic components	Benign components	Final Result	Pathogenic components	Benign components	Final Result
TECTA	R1890C	16718611 (2006)	Clinical report of 1 family with segregation	28946916 (2017)	Clinical report of 3 families with segregation	PS2, PM2, PP3, PP5	no component	Likely pathogenic	PS2_Moderate, PS4_Supporting, PM2, PP1_Strong, PP3	no component	Pathogenic
TECTA	H1400Y	22718023 (2012)	Clinical report of 1 family with segregation	23967202 (2013)	Simple clinical report without segregation	PP3, PP5	BS2	Variant of uncertain significance	PP3	BS1, BS2	Benign

^aSpecified ACMG hearing loss rules suggested by the ClinGen Hearing Loss Clinical Domain Working Group were applied [15]
Abbreviations: ACMG American College of Medical Genetics and Genomics, PMID pubmed ID, PS pathogenic strong, PM pathogenic moderate, PP pathogenic support
PS2, 1 proven de novo occurrence; PM2, absent in population databases; PP3, multiple computational evidence; PP5, recent reputable source without functional evidence; BS2, observation on in controls inconsistent with disease penetrance; PS2_Moderate, 1 proven de novo occurrence (phenotype consistent but not specific to gene); PS4_Supporting, Autosomal dominant: ≥2 probands with variant, and variant meets; PM2, Absent/rare in population databases; PP1_Strong, Segregation in one affected relative for recessive and two affected relatives for dominant; BS1, MAF of ≥0.003 (0.3%) for autosomal recessive; MAF of ≥0.0002 (0.02%) for autosomal dominant. Likely benign, provided there is no conflicting evidence

ISSN: 1471-2350