TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30974	93145;93146;93147	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
N2AB	29333	88222;88223;88224	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
N2A	28406	85441;85442;85443	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
N2B	21909	65950;65951;65952	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
Novex-1	22034	66325;66326;66327	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
Novex-2	22101	66526;66527;66528	chr2:178548706;178548705;178548704	chr2:179413433;179413432;179413431
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-150
• Domain position: 48
• Structural Position: 127
• Q(SASA): 0.3776
• 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
T/I	None	None	0.085	D	0.384	0.133	0.341226946553	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	5.65547E-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
T/A	0.0902	likely_benign	0.0783	benign	-0.933	Destabilizing	0.928	D	0.625	neutral	N	0.487298945	None	None	N
T/C	0.3751	ambiguous	0.3202	benign	-0.393	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
T/D	0.4599	ambiguous	0.425	ambiguous	0.03	Stabilizing	0.997	D	0.688	prob.neutral	None	None	None	None	N
T/E	0.3814	ambiguous	0.3459	ambiguous	0.041	Stabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	N
T/F	0.2738	likely_benign	0.2528	benign	-0.985	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
T/G	0.3086	likely_benign	0.2649	benign	-1.201	Destabilizing	0.992	D	0.661	neutral	None	None	None	None	N
T/H	0.2578	likely_benign	0.2534	benign	-1.422	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
T/I	0.1125	likely_benign	0.1033	benign	-0.306	Destabilizing	0.085	N	0.384	neutral	D	0.532654112	None	None	N
T/K	0.2459	likely_benign	0.2407	benign	-0.593	Destabilizing	0.989	D	0.686	prob.neutral	N	0.487552434	None	None	N
T/L	0.0972	likely_benign	0.0908	benign	-0.306	Destabilizing	0.745	D	0.626	neutral	None	None	None	None	N
T/M	0.092	likely_benign	0.0886	benign	0.008	Stabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
T/N	0.1275	likely_benign	0.1203	benign	-0.528	Destabilizing	0.997	D	0.703	prob.neutral	None	None	None	None	N
T/P	0.2992	likely_benign	0.2673	benign	-0.483	Destabilizing	0.996	D	0.691	prob.neutral	D	0.527613652	None	None	N
T/Q	0.2567	likely_benign	0.2409	benign	-0.659	Destabilizing	0.997	D	0.706	prob.neutral	None	None	None	None	N
T/R	0.2058	likely_benign	0.2066	benign	-0.403	Destabilizing	0.996	D	0.693	prob.neutral	N	0.496301847	None	None	N
T/S	0.1135	likely_benign	0.1042	benign	-0.867	Destabilizing	0.963	D	0.655	neutral	N	0.506371588	None	None	N
T/V	0.1013	likely_benign	0.0924	benign	-0.483	Destabilizing	0.547	D	0.628	neutral	None	None	None	None	N
T/W	0.7085	likely_pathogenic	0.6687	pathogenic	-0.9	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/Y	0.3452	ambiguous	0.3133	benign	-0.674	Destabilizing	0.992	D	0.726	prob.delet.	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.