TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23733	71422;71423;71424	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
N2AB	22092	66499;66500;66501	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
N2A	21165	63718;63719;63720	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
N2B	14668	44227;44228;44229	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
Novex-1	14793	44602;44603;44604	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
Novex-2	14860	44803;44804;44805	chr2:178574935;178574934;178574933	chr2:179439662;179439661;179439660
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-60
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.6642
• 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
P/T	None	None	1.0	N	0.779	0.454	0.453867917445	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

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
P/A	0.3191	likely_benign	0.3465	ambiguous	-0.443	Destabilizing	1.0	D	0.754	deleterious	N	0.486283489	None	None	N
P/C	0.7781	likely_pathogenic	0.826	pathogenic	-0.701	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
P/D	0.6911	likely_pathogenic	0.6956	pathogenic	-0.137	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
P/E	0.5448	ambiguous	0.5754	pathogenic	-0.236	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/F	0.8492	likely_pathogenic	0.872	pathogenic	-0.579	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
P/G	0.6871	likely_pathogenic	0.6961	pathogenic	-0.58	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/H	0.5543	ambiguous	0.5923	pathogenic	-0.09	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/I	0.6641	likely_pathogenic	0.6943	pathogenic	-0.226	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/K	0.6153	likely_pathogenic	0.673	pathogenic	-0.432	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/L	0.3991	ambiguous	0.4278	ambiguous	-0.226	Destabilizing	1.0	D	0.759	deleterious	N	0.503330425	None	None	N
P/M	0.6276	likely_pathogenic	0.6621	pathogenic	-0.427	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/N	0.6258	likely_pathogenic	0.6567	pathogenic	-0.209	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/Q	0.4706	ambiguous	0.5293	ambiguous	-0.415	Destabilizing	1.0	D	0.753	deleterious	N	0.492070387	None	None	N
P/R	0.5296	ambiguous	0.5812	pathogenic	0.045	Stabilizing	1.0	D	0.755	deleterious	N	0.506300301	None	None	N
P/S	0.4621	ambiguous	0.4876	ambiguous	-0.597	Destabilizing	1.0	D	0.781	deleterious	N	0.493044665	None	None	N
P/T	0.3419	ambiguous	0.3573	ambiguous	-0.592	Destabilizing	1.0	D	0.779	deleterious	N	0.496336348	None	None	N
P/V	0.5176	ambiguous	0.5621	ambiguous	-0.264	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/W	0.9472	likely_pathogenic	0.9488	pathogenic	-0.655	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
P/Y	0.8227	likely_pathogenic	0.8383	pathogenic	-0.364	Destabilizing	1.0	D	0.725	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.