TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35132	105619;105620;105621	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
N2AB	33491	100696;100697;100698	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
N2A	32564	97915;97916;97917	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
N2B	26067	78424;78425;78426	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
Novex-1	26192	78799;78800;78801	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
Novex-2	26259	79000;79001;79002	chr2:178531221;178531220;178531219	chr2:179395948;179395947;179395946
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-164
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2053
• 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
L/V	None	None	0.996	N	0.441	0.105	0.422404719673	gnomAD-4.0.0	6.8414E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99399E-07	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
L/A	0.824	likely_pathogenic	0.8251	pathogenic	-0.907	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
L/C	0.9372	likely_pathogenic	0.9329	pathogenic	-0.607	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/D	0.9855	likely_pathogenic	0.9869	pathogenic	-0.362	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/E	0.9079	likely_pathogenic	0.9135	pathogenic	-0.459	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/F	0.5268	ambiguous	0.5475	ambiguous	-0.926	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
L/G	0.9574	likely_pathogenic	0.9599	pathogenic	-1.086	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
L/H	0.7885	likely_pathogenic	0.8186	pathogenic	-0.343	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/I	0.1994	likely_benign	0.1789	benign	-0.552	Destabilizing	0.996	D	0.467	neutral	N	0.456131116	None	None	N
L/K	0.7667	likely_pathogenic	0.7874	pathogenic	-0.428	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
L/M	0.3368	likely_benign	0.3295	benign	-0.372	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
L/N	0.9086	likely_pathogenic	0.9116	pathogenic	-0.181	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/P	0.9576	likely_pathogenic	0.9729	pathogenic	-0.637	Destabilizing	1.0	D	0.779	deleterious	N	0.466469443	None	None	N
L/Q	0.6505	likely_pathogenic	0.6832	pathogenic	-0.468	Destabilizing	1.0	D	0.769	deleterious	N	0.499039318	None	None	N
L/R	0.639	likely_pathogenic	0.6839	pathogenic	0.197	Stabilizing	0.999	D	0.757	deleterious	N	0.476874535	None	None	N
L/S	0.8877	likely_pathogenic	0.8909	pathogenic	-0.671	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
L/T	0.7487	likely_pathogenic	0.7375	pathogenic	-0.662	Destabilizing	0.91	D	0.294	neutral	None	None	None	None	N
L/V	0.2495	likely_benign	0.2267	benign	-0.637	Destabilizing	0.996	D	0.441	neutral	N	0.430715383	None	None	N
L/W	0.7864	likely_pathogenic	0.8248	pathogenic	-0.904	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
L/Y	0.8731	likely_pathogenic	0.8839	pathogenic	-0.655	Destabilizing	1.0	D	0.759	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.