TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8366	25321;25322;25323	chr2:178717778;178717777;178717776	chr2:179582505;179582504;179582503
N2AB	8049	24370;24371;24372	chr2:178717778;178717777;178717776	chr2:179582505;179582504;179582503
N2A	7122	21589;21590;21591	chr2:178717778;178717777;178717776	chr2:179582505;179582504;179582503
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-69
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.128
• 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/P	None	None	1.0	N	0.874	0.441	0.663968203398	gnomAD-4.0.0	1.60519E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45151E-05	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	0.8703	likely_pathogenic	0.8795	pathogenic	-2.119	Highly Destabilizing	0.997	D	0.533	neutral	None	None	None	None	N
L/C	0.9492	likely_pathogenic	0.9487	pathogenic	-1.473	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.9982	pathogenic	-1.691	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/E	0.9816	likely_pathogenic	0.9858	pathogenic	-1.51	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/F	0.8148	likely_pathogenic	0.8278	pathogenic	-1.234	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/G	0.9724	likely_pathogenic	0.9779	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/H	0.9856	likely_pathogenic	0.9898	pathogenic	-1.979	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/I	0.241	likely_benign	0.2066	benign	-0.686	Destabilizing	0.924	D	0.507	neutral	None	None	None	None	N
L/K	0.9836	likely_pathogenic	0.9868	pathogenic	-1.292	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
L/M	0.3341	likely_benign	0.3185	benign	-0.716	Destabilizing	0.998	D	0.739	prob.delet.	N	0.452238031	None	None	N
L/N	0.983	likely_pathogenic	0.987	pathogenic	-1.449	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/P	0.7654	likely_pathogenic	0.7432	pathogenic	-1.14	Destabilizing	1.0	D	0.874	deleterious	N	0.474551013	None	None	N
L/Q	0.9371	likely_pathogenic	0.9537	pathogenic	-1.369	Destabilizing	1.0	D	0.861	deleterious	N	0.478824982	None	None	N
L/R	0.9692	likely_pathogenic	0.9775	pathogenic	-1.058	Destabilizing	1.0	D	0.849	deleterious	N	0.501448687	None	None	N
L/S	0.9792	likely_pathogenic	0.9838	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
L/T	0.9174	likely_pathogenic	0.9239	pathogenic	-1.928	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
L/V	0.279	likely_benign	0.2321	benign	-1.14	Destabilizing	0.154	N	0.267	neutral	N	0.441513609	None	None	N
L/W	0.9644	likely_pathogenic	0.9737	pathogenic	-1.486	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/Y	0.9832	likely_pathogenic	0.9869	pathogenic	-1.187	Destabilizing	1.0	D	0.805	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.