TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13908	41947;41948;41949	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
N2AB	12267	37024;37025;37026	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
N2A	11340	34243;34244;34245	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
N2B	4843	14752;14753;14754	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
Novex-1	4968	15127;15128;15129	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
Novex-2	5035	15328;15329;15330	chr2:178635602;178635601;178635600	chr2:179500329;179500328;179500327
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: Ig-89
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.3753
• 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	0.007	N	0.286	0.112	0.173771789658	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	0.8234	likely_pathogenic	0.8023	pathogenic	-0.948	Destabilizing	0.74	D	0.487	neutral	None	None	None	None	N
K/C	0.8065	likely_pathogenic	0.8055	pathogenic	-0.891	Destabilizing	0.996	D	0.733	deleterious	None	None	None	None	N
K/D	0.9741	likely_pathogenic	0.9671	pathogenic	-0.191	Destabilizing	0.909	D	0.634	neutral	None	None	None	None	N
K/E	0.7531	likely_pathogenic	0.6949	pathogenic	-0.034	Destabilizing	0.682	D	0.432	neutral	D	0.575934369	None	None	N
K/F	0.9447	likely_pathogenic	0.9395	pathogenic	-0.629	Destabilizing	0.996	D	0.727	deleterious	None	None	None	None	N
K/G	0.9337	likely_pathogenic	0.9243	pathogenic	-1.342	Destabilizing	0.909	D	0.584	neutral	None	None	None	None	N
K/H	0.4801	ambiguous	0.4676	ambiguous	-1.625	Destabilizing	0.987	D	0.588	neutral	None	None	None	None	N
K/I	0.7393	likely_pathogenic	0.6836	pathogenic	0.096	Stabilizing	0.938	D	0.754	deleterious	D	0.573036806	None	None	N
K/L	0.6446	likely_pathogenic	0.5902	pathogenic	0.096	Stabilizing	0.909	D	0.584	neutral	None	None	None	None	N
K/M	0.585	likely_pathogenic	0.5437	ambiguous	-0.036	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	N
K/N	0.9042	likely_pathogenic	0.8873	pathogenic	-0.69	Destabilizing	0.883	D	0.605	neutral	D	0.575934369	None	None	N
K/P	0.9924	likely_pathogenic	0.9908	pathogenic	-0.223	Destabilizing	0.953	D	0.629	neutral	None	None	None	None	N
K/Q	0.3569	ambiguous	0.3214	benign	-0.676	Destabilizing	0.883	D	0.599	neutral	D	0.575206445	None	None	N
K/R	0.0791	likely_benign	0.0778	benign	-0.612	Destabilizing	0.007	N	0.286	neutral	N	0.500342548	None	None	N
K/S	0.8725	likely_pathogenic	0.8598	pathogenic	-1.436	Destabilizing	0.74	D	0.54	neutral	None	None	None	None	N
K/T	0.7581	likely_pathogenic	0.7105	pathogenic	-1.045	Destabilizing	0.883	D	0.611	neutral	D	0.575206445	None	None	N
K/V	0.6862	likely_pathogenic	0.6588	pathogenic	-0.223	Destabilizing	0.909	D	0.693	prob.delet.	None	None	None	None	N
K/W	0.9085	likely_pathogenic	0.8949	pathogenic	-0.472	Destabilizing	0.996	D	0.668	prob.neutral	None	None	None	None	N
K/Y	0.8437	likely_pathogenic	0.8412	pathogenic	-0.174	Destabilizing	0.984	D	0.706	prob.delet.	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.