TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32590	97993;97994;97995	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
N2AB	30949	93070;93071;93072	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
N2A	30022	90289;90290;90291	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
N2B	23525	70798;70799;70800	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
Novex-1	23650	71173;71174;71175	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
Novex-2	23717	71374;71375;71376	chr2:178541309;178541308;178541307	chr2:179406036;179406035;179406034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-125
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8114
• Predicted PPI site: I

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
K/N	None	None	0.501	N	0.415	0.051	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
K/A	0.2714	likely_benign	0.3393	benign	0.025	Stabilizing	0.018	N	0.266	neutral	None	None	None	None	I
K/C	0.6523	likely_pathogenic	0.7127	pathogenic	-0.454	Destabilizing	0.991	D	0.446	neutral	None	None	None	None	I
K/D	0.4009	ambiguous	0.5044	ambiguous	-0.234	Destabilizing	0.004	N	0.272	neutral	None	None	None	None	I
K/E	0.1593	likely_benign	0.213	benign	-0.234	Destabilizing	0.172	N	0.478	neutral	N	0.365672188	None	None	I
K/F	0.6663	likely_pathogenic	0.741	pathogenic	-0.304	Destabilizing	0.905	D	0.469	neutral	None	None	None	None	I
K/G	0.3659	ambiguous	0.4542	ambiguous	-0.112	Destabilizing	0.571	D	0.445	neutral	None	None	None	None	I
K/H	0.3203	likely_benign	0.3662	ambiguous	-0.19	Destabilizing	0.973	D	0.383	neutral	None	None	None	None	I
K/I	0.3193	likely_benign	0.3804	ambiguous	0.302	Stabilizing	0.638	D	0.495	neutral	N	0.504295996	None	None	I
K/L	0.2883	likely_benign	0.3457	ambiguous	0.302	Stabilizing	0.4	N	0.474	neutral	None	None	None	None	I
K/M	0.2442	likely_benign	0.2994	benign	-0.147	Destabilizing	0.905	D	0.381	neutral	None	None	None	None	I
K/N	0.3447	ambiguous	0.4361	ambiguous	0.007	Stabilizing	0.501	D	0.415	neutral	N	0.450058867	None	None	I
K/P	0.3777	ambiguous	0.4537	ambiguous	0.233	Stabilizing	0.905	D	0.494	neutral	None	None	None	None	I
K/Q	0.1353	likely_benign	0.1545	benign	-0.097	Destabilizing	0.03	N	0.293	neutral	N	0.434956128	None	None	I
K/R	0.0908	likely_benign	0.0954	benign	-0.063	Destabilizing	0.335	N	0.49	neutral	N	0.441343383	None	None	I
K/S	0.3266	likely_benign	0.4115	ambiguous	-0.344	Destabilizing	0.4	N	0.381	neutral	None	None	None	None	I
K/T	0.1873	likely_benign	0.2355	benign	-0.222	Destabilizing	0.501	D	0.38	neutral	N	0.471124785	None	None	I
K/V	0.2757	likely_benign	0.3396	benign	0.233	Stabilizing	0.018	N	0.344	neutral	None	None	None	None	I
K/W	0.7013	likely_pathogenic	0.7763	pathogenic	-0.427	Destabilizing	0.991	D	0.525	neutral	None	None	None	None	I
K/Y	0.5451	ambiguous	0.6272	pathogenic	-0.069	Destabilizing	0.905	D	0.493	neutral	None	None	None	None	I

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.