TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20583	61972;61973;61974	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
N2AB	18942	57049;57050;57051	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
N2A	18015	54268;54269;54270	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
N2B	11518	34777;34778;34779	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
Novex-1	11643	35152;35153;35154	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
Novex-2	11710	35353;35354;35355	chr2:178589978;178589977;178589976	chr2:179454705;179454704;179454703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-37
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4994
• 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
K/R	None	None	0.884	N	0.334	0.173	0.202949470691	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
K/A	0.55	ambiguous	0.5031	ambiguous	-0.329	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	N
K/C	0.899	likely_pathogenic	0.884	pathogenic	-0.418	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/D	0.8753	likely_pathogenic	0.8147	pathogenic	-0.424	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/E	0.4234	ambiguous	0.2949	benign	-0.4	Destabilizing	0.996	D	0.551	neutral	N	0.505221503	None	None	N
K/F	0.9659	likely_pathogenic	0.9527	pathogenic	-0.563	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/G	0.6856	likely_pathogenic	0.6218	pathogenic	-0.589	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/H	0.6786	likely_pathogenic	0.6416	pathogenic	-1.1	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
K/I	0.7756	likely_pathogenic	0.6806	pathogenic	0.295	Stabilizing	1.0	D	0.755	deleterious	N	0.47278759	None	None	N
K/L	0.7242	likely_pathogenic	0.6455	pathogenic	0.295	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
K/M	0.5659	likely_pathogenic	0.4738	ambiguous	0.461	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/N	0.7783	likely_pathogenic	0.6785	pathogenic	-0.17	Destabilizing	0.999	D	0.705	prob.neutral	N	0.51567057	None	None	N
K/P	0.8551	likely_pathogenic	0.777	pathogenic	0.116	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/Q	0.2665	likely_benign	0.2288	benign	-0.483	Destabilizing	0.999	D	0.703	prob.neutral	N	0.471938216	None	None	N
K/R	0.1004	likely_benign	0.0957	benign	-0.264	Destabilizing	0.884	D	0.334	neutral	N	0.508821955	None	None	N
K/S	0.6445	likely_pathogenic	0.5871	pathogenic	-0.725	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
K/T	0.4787	ambiguous	0.3715	ambiguous	-0.538	Destabilizing	0.999	D	0.672	neutral	N	0.468099874	None	None	N
K/V	0.676	likely_pathogenic	0.5903	pathogenic	0.116	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.9483	likely_pathogenic	0.9279	pathogenic	-0.471	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/Y	0.8998	likely_pathogenic	0.8684	pathogenic	-0.087	Destabilizing	1.0	D	0.741	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.