TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2464	7615;7616;7617	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
N2AB	2464	7615;7616;7617	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
N2A	2464	7615;7616;7617	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
N2B	2418	7477;7478;7479	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
Novex-1	2418	7477;7478;7479	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
Novex-2	2418	7477;7478;7479	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391
Novex-3	2464	7615;7616;7617	chr2:178773666;178773665;178773664	chr2:179638393;179638392;179638391

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-14
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1036
• 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/H	None	None	1.0	D	0.858	0.852	0.926469043632	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
L/A	0.8443	likely_pathogenic	0.827	pathogenic	-2.554	Highly Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
L/C	0.8203	likely_pathogenic	0.7967	pathogenic	-1.763	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/D	0.998	likely_pathogenic	0.9976	pathogenic	-3.43	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/E	0.9858	likely_pathogenic	0.9839	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/F	0.1192	likely_benign	0.1129	benign	-1.647	Destabilizing	1.0	D	0.785	deleterious	N	0.512858401	None	None	N
L/G	0.9708	likely_pathogenic	0.967	pathogenic	-3.09	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9333	likely_pathogenic	0.9244	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.770609436	None	None	N
L/I	0.178	likely_benign	0.17	benign	-0.95	Destabilizing	0.999	D	0.605	neutral	D	0.660348623	None	None	N
L/K	0.9753	likely_pathogenic	0.9731	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/M	0.147	likely_benign	0.1416	benign	-0.958	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/N	0.9878	likely_pathogenic	0.9858	pathogenic	-2.763	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/P	0.9887	likely_pathogenic	0.9885	pathogenic	-1.475	Destabilizing	1.0	D	0.892	deleterious	D	0.770609436	None	None	N
L/Q	0.9292	likely_pathogenic	0.9224	pathogenic	-2.506	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/R	0.952	likely_pathogenic	0.9477	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.770609436	None	None	N
L/S	0.9629	likely_pathogenic	0.9565	pathogenic	-3.279	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/T	0.9093	likely_pathogenic	0.8964	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/V	0.2287	likely_benign	0.2172	benign	-1.475	Destabilizing	0.999	D	0.63	neutral	D	0.735169275	None	None	N
L/W	0.629	likely_pathogenic	0.6085	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/Y	0.7416	likely_pathogenic	0.7201	pathogenic	-1.758	Destabilizing	1.0	D	0.823	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.