TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18776	56551;56552;56553	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
N2AB	17135	51628;51629;51630	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
N2A	16208	48847;48848;48849	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
N2B	9711	29356;29357;29358	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
Novex-1	9836	29731;29732;29733	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
Novex-2	9903	29932;29933;29934	chr2:178599575;178599574;178599573	chr2:179464302;179464301;179464300
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-116
• Domain position: 89
• Structural Position: 171
• Q(SASA): 0.5012
• 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
E/K	rs987030753	None	0.92	N	0.479	0.25	0.319114376414	gnomAD-4.0.0	1.65905E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.54226E-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
E/A	0.2642	likely_benign	0.2311	benign	-0.587	Destabilizing	0.134	N	0.23	neutral	N	0.503814073	None	None	I
E/C	0.9253	likely_pathogenic	0.9099	pathogenic	-0.297	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
E/D	0.2473	likely_benign	0.1931	benign	-0.861	Destabilizing	0.015	N	0.161	neutral	N	0.464218321	None	None	I
E/F	0.921	likely_pathogenic	0.9005	pathogenic	-0.069	Destabilizing	0.997	D	0.656	neutral	None	None	None	None	I
E/G	0.359	ambiguous	0.2877	benign	-0.921	Destabilizing	0.826	D	0.569	neutral	D	0.528653802	None	None	I
E/H	0.7692	likely_pathogenic	0.7112	pathogenic	-0.209	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	I
E/I	0.5595	ambiguous	0.5169	ambiguous	0.308	Stabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	I
E/K	0.4101	ambiguous	0.3314	benign	-0.232	Destabilizing	0.92	D	0.479	neutral	N	0.494365083	None	None	I
E/L	0.6981	likely_pathogenic	0.6455	pathogenic	0.308	Stabilizing	0.939	D	0.675	prob.neutral	None	None	None	None	I
E/M	0.6528	likely_pathogenic	0.6114	pathogenic	0.563	Stabilizing	0.999	D	0.633	neutral	None	None	None	None	I
E/N	0.4799	ambiguous	0.4047	ambiguous	-0.756	Destabilizing	0.939	D	0.506	neutral	None	None	None	None	I
E/P	0.7502	likely_pathogenic	0.6725	pathogenic	0.032	Stabilizing	0.991	D	0.651	neutral	None	None	None	None	I
E/Q	0.255	likely_benign	0.2178	benign	-0.625	Destabilizing	0.959	D	0.555	neutral	N	0.495984023	None	None	I
E/R	0.6258	likely_pathogenic	0.5324	ambiguous	0.049	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	I
E/S	0.3682	ambiguous	0.3043	benign	-0.984	Destabilizing	0.2	N	0.151	neutral	None	None	None	None	I
E/T	0.334	likely_benign	0.273	benign	-0.706	Destabilizing	0.884	D	0.551	neutral	None	None	None	None	I
E/V	0.333	likely_benign	0.2984	benign	0.032	Stabilizing	0.92	D	0.667	neutral	N	0.511857553	None	None	I
E/W	0.974	likely_pathogenic	0.964	pathogenic	0.166	Stabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
E/Y	0.8449	likely_pathogenic	0.8038	pathogenic	0.184	Stabilizing	0.997	D	0.645	neutral	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.