TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17082	51469;51470;51471	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
N2AB	15441	46546;46547;46548	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
N2A	14514	43765;43766;43767	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
N2B	8017	24274;24275;24276	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
Novex-1	8142	24649;24650;24651	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
Novex-2	8209	24850;24851;24852	chr2:178610282;178610281;178610280	chr2:179475009;179475008;179475007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-12
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1068
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Y/C	None	None	1.0	D	0.884	0.915	0.890879712393	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/F	None	None	0.999	D	0.636	0.801	0.717669958738	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Y/A	0.998	likely_pathogenic	0.9972	pathogenic	-3.722	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/C	0.9534	likely_pathogenic	0.9351	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.830981411	None	None	N
Y/D	0.9983	likely_pathogenic	0.9977	pathogenic	-3.851	Highly Destabilizing	1.0	D	0.916	deleterious	D	0.829988606	None	None	N
Y/E	0.9995	likely_pathogenic	0.9994	pathogenic	-3.678	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/F	0.3211	likely_benign	0.2407	benign	-1.555	Destabilizing	0.999	D	0.636	neutral	D	0.658007306	None	None	N
Y/G	0.9944	likely_pathogenic	0.9939	pathogenic	-4.055	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
Y/H	0.9775	likely_pathogenic	0.9689	pathogenic	-2.601	Highly Destabilizing	1.0	D	0.799	deleterious	D	0.762015094	None	None	N
Y/I	0.9888	likely_pathogenic	0.9818	pathogenic	-2.571	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9989	pathogenic	-2.714	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.9706	likely_pathogenic	0.9607	pathogenic	-2.571	Highly Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
Y/M	0.9918	likely_pathogenic	0.9874	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/N	0.988	likely_pathogenic	0.9853	pathogenic	-3.357	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.829988606	None	None	N
Y/P	0.9993	likely_pathogenic	0.9991	pathogenic	-2.975	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9985	pathogenic	-3.182	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/R	0.9962	likely_pathogenic	0.9952	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/S	0.992	likely_pathogenic	0.9892	pathogenic	-3.678	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.829988606	None	None	N
Y/T	0.9964	likely_pathogenic	0.9949	pathogenic	-3.416	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.9741	likely_pathogenic	0.9607	pathogenic	-2.975	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
Y/W	0.8726	likely_pathogenic	0.8329	pathogenic	-0.869	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.