TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2167	6724;6725;6726	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
N2AB	2167	6724;6725;6726	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
N2A	2167	6724;6725;6726	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
N2B	2121	6586;6587;6588	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
Novex-1	2121	6586;6587;6588	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
Novex-2	2121	6586;6587;6588	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090
Novex-3	2167	6724;6725;6726	chr2:178775365;178775364;178775363	chr2:179640092;179640091;179640090

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-10
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.4332
• 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/F	None	None	1.0	N	0.654	0.342	0.798223434742	gnomAD-4.0.0	2.05238E-06	None	None	None	None	N	None	0	0	None	0	2.52092E-05	None	0	0	1.79861E-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	0.8586	likely_pathogenic	0.9169	pathogenic	-1.235	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
L/C	0.9611	likely_pathogenic	0.9782	pathogenic	-0.887	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
L/D	0.9894	likely_pathogenic	0.9947	pathogenic	-0.348	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/E	0.9556	likely_pathogenic	0.9769	pathogenic	-0.377	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/F	0.6629	likely_pathogenic	0.7831	pathogenic	-0.883	Destabilizing	1.0	D	0.654	neutral	N	0.502675408	None	None	N
L/G	0.9732	likely_pathogenic	0.9865	pathogenic	-1.504	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/H	0.8697	likely_pathogenic	0.9238	pathogenic	-0.666	Destabilizing	1.0	D	0.728	prob.delet.	N	0.509954182	None	None	N
L/I	0.3288	likely_benign	0.4244	ambiguous	-0.602	Destabilizing	0.999	D	0.485	neutral	N	0.494514319	None	None	N
L/K	0.8897	likely_pathogenic	0.9275	pathogenic	-0.693	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
L/M	0.3994	ambiguous	0.4837	ambiguous	-0.531	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
L/N	0.9349	likely_pathogenic	0.9645	pathogenic	-0.517	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/P	0.9907	likely_pathogenic	0.9952	pathogenic	-0.779	Destabilizing	1.0	D	0.758	deleterious	D	0.616915564	None	None	N
L/Q	0.8238	likely_pathogenic	0.897	pathogenic	-0.71	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/R	0.819	likely_pathogenic	0.8783	pathogenic	-0.14	Destabilizing	1.0	D	0.766	deleterious	N	0.501397917	None	None	N
L/S	0.9386	likely_pathogenic	0.9704	pathogenic	-1.153	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/T	0.8418	likely_pathogenic	0.9053	pathogenic	-1.065	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/V	0.3848	ambiguous	0.5153	ambiguous	-0.779	Destabilizing	0.999	D	0.527	neutral	N	0.500082925	None	None	N
L/W	0.8882	likely_pathogenic	0.9398	pathogenic	-0.885	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/Y	0.8998	likely_pathogenic	0.9411	pathogenic	-0.651	Destabilizing	1.0	D	0.728	prob.delet.	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.