TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4024	12295;12296;12297	chr2:178741163;178741162;178741161	chr2:179605890;179605889;179605888
N2AB	3707	11344;11345;11346	chr2:178741163;178741162;178741161	chr2:179605890;179605889;179605888
N2A	None	None	chr2:None	chr2:None
N2B	3661	11206;11207;11208	chr2:178741163;178741162;178741161	chr2:179605890;179605889;179605888
Novex-1	3786	11581;11582;11583	chr2:178741163;178741162;178741161	chr2:179605890;179605889;179605888
Novex-2	3853	11782;11783;11784	chr2:178741163;178741162;178741161	chr2:179605890;179605889;179605888
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-28
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.1257
• Predicted PPI site: I

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
A/T	None	None	0.977	D	0.675	0.418	None	gnomAD-4.0.0	3.42172E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59774E-06	1.15934E-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
A/C	0.7626	likely_pathogenic	0.7544	pathogenic	-0.752	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
A/D	0.9199	likely_pathogenic	0.8721	pathogenic	-1.732	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	I
A/E	0.8848	likely_pathogenic	0.8184	pathogenic	-1.554	Destabilizing	0.997	D	0.849	deleterious	D	0.695573458	None	None	I
A/F	0.9154	likely_pathogenic	0.8699	pathogenic	-0.562	Destabilizing	0.995	D	0.899	deleterious	None	None	None	None	I
A/G	0.2774	likely_benign	0.2796	benign	-1.332	Destabilizing	0.989	D	0.621	neutral	D	0.52321945	None	None	I
A/H	0.965	likely_pathogenic	0.9434	pathogenic	-1.767	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
A/I	0.7856	likely_pathogenic	0.7641	pathogenic	0.379	Stabilizing	0.966	D	0.787	deleterious	None	None	None	None	I
A/K	0.9528	likely_pathogenic	0.9174	pathogenic	-1.095	Destabilizing	0.998	D	0.853	deleterious	None	None	None	None	I
A/L	0.7293	likely_pathogenic	0.6752	pathogenic	0.379	Stabilizing	0.966	D	0.655	neutral	None	None	None	None	I
A/M	0.7419	likely_pathogenic	0.7087	pathogenic	0.238	Stabilizing	0.999	D	0.861	deleterious	None	None	None	None	I
A/N	0.8988	likely_pathogenic	0.8661	pathogenic	-1.251	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	I
A/P	0.9668	likely_pathogenic	0.9547	pathogenic	0.012	Stabilizing	0.999	D	0.877	deleterious	D	0.733867162	None	None	I
A/Q	0.9001	likely_pathogenic	0.8507	pathogenic	-1.08	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	I
A/R	0.903	likely_pathogenic	0.8404	pathogenic	-1.187	Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	I
A/S	0.2006	likely_benign	0.212	benign	-1.696	Destabilizing	0.989	D	0.633	neutral	D	0.590506967	None	None	I
A/T	0.2432	likely_benign	0.2562	benign	-1.382	Destabilizing	0.977	D	0.675	neutral	D	0.566074726	None	None	I
A/V	0.4056	ambiguous	0.3872	ambiguous	0.012	Stabilizing	0.235	N	0.414	neutral	N	0.51480646	None	None	I
A/W	0.9879	likely_pathogenic	0.9797	pathogenic	-1.308	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
A/Y	0.9605	likely_pathogenic	0.9364	pathogenic	-0.691	Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	I

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.