TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33460	100603;100604;100605	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
N2AB	31819	95680;95681;95682	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
N2A	30892	92899;92900;92901	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
N2B	24395	73408;73409;73410	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
Novex-1	24520	73783;73784;73785	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
Novex-2	24587	73984;73985;73986	chr2:178536369;178536368;178536367	chr2:179401096;179401095;179401094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-131
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.364
• 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
G/D	rs1691502761	None	0.153	N	0.603	0.319	0.177238962908	gnomAD-4.0.0	1.59153E-06	None	None	None	None	N	None	5.65803E-05	0	None	0	0	None	0	0	0	0	0
G/S	rs1177814135	None	0.978	N	0.79	0.393	0.32306181527	gnomAD-4.0.0	3.18305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	3.0248E-05

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
G/A	0.4375	ambiguous	0.4458	ambiguous	-0.494	Destabilizing	0.961	D	0.716	prob.delet.	N	0.482798585	None	None	N
G/C	0.4741	ambiguous	0.5098	ambiguous	-0.931	Destabilizing	1.0	D	0.858	deleterious	D	0.532391317	None	None	N
G/D	0.2496	likely_benign	0.2817	benign	-1.032	Destabilizing	0.153	N	0.603	neutral	N	0.485990742	None	None	N
G/E	0.4131	ambiguous	0.4606	ambiguous	-1.164	Destabilizing	0.983	D	0.857	deleterious	None	None	None	None	N
G/F	0.864	likely_pathogenic	0.8655	pathogenic	-1.033	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/H	0.6956	likely_pathogenic	0.7044	pathogenic	-0.827	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
G/I	0.7709	likely_pathogenic	0.8175	pathogenic	-0.459	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
G/K	0.7654	likely_pathogenic	0.8058	pathogenic	-1.245	Destabilizing	0.991	D	0.871	deleterious	None	None	None	None	N
G/L	0.8365	likely_pathogenic	0.8363	pathogenic	-0.459	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
G/M	0.8384	likely_pathogenic	0.8338	pathogenic	-0.489	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
G/N	0.3115	likely_benign	0.3058	benign	-0.854	Destabilizing	0.983	D	0.83	deleterious	None	None	None	None	N
G/P	0.9814	likely_pathogenic	0.9813	pathogenic	-0.434	Destabilizing	0.996	D	0.877	deleterious	None	None	None	None	N
G/Q	0.6437	likely_pathogenic	0.6635	pathogenic	-1.129	Destabilizing	0.991	D	0.885	deleterious	None	None	None	None	N
G/R	0.6961	likely_pathogenic	0.7623	pathogenic	-0.732	Destabilizing	0.989	D	0.887	deleterious	N	0.513019614	None	None	N
G/S	0.2243	likely_benign	0.2243	benign	-0.984	Destabilizing	0.978	D	0.79	deleterious	N	0.484747142	None	None	N
G/T	0.482	ambiguous	0.4974	ambiguous	-1.051	Destabilizing	0.991	D	0.87	deleterious	None	None	None	None	N
G/V	0.6538	likely_pathogenic	0.7125	pathogenic	-0.434	Destabilizing	0.994	D	0.87	deleterious	D	0.531884338	None	None	N
G/W	0.7751	likely_pathogenic	0.8118	pathogenic	-1.251	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
G/Y	0.7215	likely_pathogenic	0.738	pathogenic	-0.907	Destabilizing	1.0	D	0.859	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.