TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19008	57247;57248;57249	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
N2AB	17367	52324;52325;52326	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
N2A	16440	49543;49544;49545	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
N2B	9943	30052;30053;30054	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
Novex-1	10068	30427;30428;30429	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
Novex-2	10135	30628;30629;30630	chr2:178598595;178598594;178598593	chr2:179463322;179463321;179463320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-26
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3523
• 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
E/K	None	None	0.999	N	0.603	0.37	0.37262878642	gnomAD-4.0.0	1.60466E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86812E-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
E/A	0.2028	likely_benign	0.191	benign	-1.103	Destabilizing	0.999	D	0.706	prob.neutral	N	0.435711063	None	None	N
E/C	0.8536	likely_pathogenic	0.8246	pathogenic	-0.645	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/D	0.4294	ambiguous	0.3945	ambiguous	-1.264	Destabilizing	0.999	D	0.518	neutral	N	0.504648287	None	None	N
E/F	0.8618	likely_pathogenic	0.8314	pathogenic	-0.54	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
E/G	0.3704	ambiguous	0.3572	ambiguous	-1.496	Destabilizing	1.0	D	0.779	deleterious	N	0.476096248	None	None	N
E/H	0.767	likely_pathogenic	0.7169	pathogenic	-0.836	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.4298	ambiguous	0.3964	ambiguous	-0.011	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
E/K	0.5129	ambiguous	0.4812	ambiguous	-0.98	Destabilizing	0.999	D	0.603	neutral	N	0.444618548	None	None	N
E/L	0.563	ambiguous	0.5249	ambiguous	-0.011	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
E/M	0.5531	ambiguous	0.52	ambiguous	0.536	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/N	0.6075	likely_pathogenic	0.5751	pathogenic	-1.377	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/P	0.9948	likely_pathogenic	0.9928	pathogenic	-0.355	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
E/Q	0.2028	likely_benign	0.1894	benign	-1.226	Destabilizing	1.0	D	0.688	prob.neutral	N	0.452525956	None	None	N
E/R	0.6454	likely_pathogenic	0.5972	pathogenic	-0.698	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/S	0.2943	likely_benign	0.273	benign	-1.807	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
E/T	0.2872	likely_benign	0.2572	benign	-1.477	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/V	0.2709	likely_benign	0.2499	benign	-0.355	Destabilizing	1.0	D	0.851	deleterious	N	0.474461453	None	None	N
E/W	0.9708	likely_pathogenic	0.9597	pathogenic	-0.31	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/Y	0.8386	likely_pathogenic	0.8005	pathogenic	-0.29	Destabilizing	1.0	D	0.891	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.