TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1927	6004;6005;6006	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
N2AB	1927	6004;6005;6006	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
N2A	1927	6004;6005;6006	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
N2B	1881	5866;5867;5868	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
Novex-1	1881	5866;5867;5868	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
Novex-2	1881	5866;5867;5868	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810
Novex-3	1927	6004;6005;6006	chr2:178776085;178776084;178776083	chr2:179640812;179640811;179640810

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-9
• Domain position: 87
• Structural Position: 174
• Q(SASA): 0.1582
• 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	0.999	D	0.895	0.761	0.774520175461	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	2.77239E-05	None	0	0	0	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	0.9661	likely_pathogenic	0.9689	pathogenic	-3.061	Highly Destabilizing	0.983	D	0.723	prob.delet.	None	None	None	None	N
L/C	0.9467	likely_pathogenic	0.9417	pathogenic	-2.325	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.419	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/E	0.9979	likely_pathogenic	0.9983	pathogenic	-3.14	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
L/F	0.7045	likely_pathogenic	0.66	pathogenic	-1.808	Destabilizing	0.993	D	0.83	deleterious	D	0.730378999	None	None	N
L/G	0.9949	likely_pathogenic	0.9956	pathogenic	-3.661	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/H	0.9964	likely_pathogenic	0.9966	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.733724328	None	None	N
L/I	0.3118	likely_benign	0.2893	benign	-1.282	Destabilizing	0.117	N	0.311	neutral	N	0.520155807	None	None	N
L/K	0.9964	likely_pathogenic	0.997	pathogenic	-2.423	Highly Destabilizing	0.998	D	0.886	deleterious	None	None	None	None	N
L/M	0.3436	ambiguous	0.348	ambiguous	-1.293	Destabilizing	0.995	D	0.8	deleterious	None	None	None	None	N
L/N	0.9983	likely_pathogenic	0.9983	pathogenic	-2.922	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/P	0.9986	likely_pathogenic	0.9989	pathogenic	-1.861	Destabilizing	0.999	D	0.895	deleterious	D	0.733724328	None	None	N
L/Q	0.9941	likely_pathogenic	0.9955	pathogenic	-2.706	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/R	0.9931	likely_pathogenic	0.9946	pathogenic	-2.147	Highly Destabilizing	0.999	D	0.884	deleterious	D	0.733724328	None	None	N
L/S	0.9977	likely_pathogenic	0.9977	pathogenic	-3.648	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/T	0.9727	likely_pathogenic	0.9762	pathogenic	-3.213	Highly Destabilizing	0.995	D	0.845	deleterious	None	None	None	None	N
L/V	0.3932	ambiguous	0.3727	ambiguous	-1.861	Destabilizing	0.898	D	0.67	neutral	N	0.498508951	None	None	N
L/W	0.9778	likely_pathogenic	0.9791	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9813	likely_pathogenic	0.9781	pathogenic	-1.97	Destabilizing	0.999	D	0.855	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.