TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21713	65362;65363;65364	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
N2AB	20072	60439;60440;60441	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
N2A	19145	57658;57659;57660	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
N2B	12648	38167;38168;38169	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
Novex-1	12773	38542;38543;38544	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
Novex-2	12840	38743;38744;38745	chr2:178584414;178584413;178584412	chr2:179449141;179449140;179449139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-45
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.2141
• 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/F	rs759672249	-1.336	0.171	N	0.419	0.133	0.239901079897	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
L/F	rs759672249	-1.336	0.171	N	0.419	0.133	0.239901079897	gnomAD-4.0.0	1.59227E-06	None	None	None	None	N	None	0	2.28739E-05	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
L/A	0.1317	likely_benign	0.1089	benign	-1.478	Destabilizing	None	N	0.22	neutral	None	None	None	None	N
L/C	0.4762	ambiguous	0.41	ambiguous	-0.915	Destabilizing	0.676	D	0.365	neutral	None	None	None	None	N
L/D	0.7506	likely_pathogenic	0.7033	pathogenic	-0.59	Destabilizing	0.214	N	0.431	neutral	None	None	None	None	N
L/E	0.4243	ambiguous	0.3869	ambiguous	-0.568	Destabilizing	0.072	N	0.418	neutral	None	None	None	None	N
L/F	0.2386	likely_benign	0.2049	benign	-0.928	Destabilizing	0.171	N	0.419	neutral	N	0.47261346	None	None	N
L/G	0.5575	ambiguous	0.4585	ambiguous	-1.817	Destabilizing	0.038	N	0.359	neutral	None	None	None	None	N
L/H	0.3399	likely_benign	0.2931	benign	-0.966	Destabilizing	0.828	D	0.429	neutral	N	0.510883613	None	None	N
L/I	0.082	likely_benign	0.0755	benign	-0.625	Destabilizing	None	N	0.225	neutral	N	0.477576329	None	None	N
L/K	0.3772	ambiguous	0.3435	ambiguous	-0.912	Destabilizing	0.072	N	0.381	neutral	None	None	None	None	N
L/M	0.1197	likely_benign	0.1097	benign	-0.539	Destabilizing	0.214	N	0.449	neutral	None	None	None	None	N
L/N	0.4031	ambiguous	0.3372	benign	-0.759	Destabilizing	0.214	N	0.412	neutral	None	None	None	None	N
L/P	0.0821	likely_benign	0.0708	benign	-0.877	Destabilizing	None	N	0.362	neutral	N	0.404486866	None	None	N
L/Q	0.2211	likely_benign	0.1886	benign	-0.876	Destabilizing	0.356	N	0.381	neutral	None	None	None	None	N
L/R	0.3101	likely_benign	0.281	benign	-0.395	Destabilizing	0.295	N	0.361	neutral	N	0.502128057	None	None	N
L/S	0.2829	likely_benign	0.2156	benign	-1.438	Destabilizing	0.003	N	0.347	neutral	None	None	None	None	N
L/T	0.1519	likely_benign	0.1218	benign	-1.288	Destabilizing	0.038	N	0.347	neutral	None	None	None	None	N
L/V	0.0804	likely_benign	0.0682	benign	-0.877	Destabilizing	None	N	0.119	neutral	N	0.443036894	None	None	N
L/W	0.4351	ambiguous	0.3895	ambiguous	-0.991	Destabilizing	0.864	D	0.433	neutral	None	None	None	None	N
L/Y	0.4436	ambiguous	0.4065	ambiguous	-0.761	Destabilizing	0.356	N	0.378	neutral	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.