TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17725	53398;53399;53400	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
N2AB	16084	48475;48476;48477	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
N2A	15157	45694;45695;45696	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
N2B	8660	26203;26204;26205	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
Novex-1	8785	26578;26579;26580	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
Novex-2	8852	26779;26780;26781	chr2:178607515;178607514;178607513	chr2:179472242;179472241;179472240
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-113
• Domain position: 49
• Structural Position: 134
• Q(SASA): 0.5123
• 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
T/I	None	None	0.927	N	0.447	0.278	0.437207349437	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	0	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
T/A	0.0975	likely_benign	0.0943	benign	-0.446	Destabilizing	0.27	N	0.247	neutral	N	0.496095879	None	None	N
T/C	0.4616	ambiguous	0.4965	ambiguous	-0.289	Destabilizing	0.995	D	0.452	neutral	None	None	None	None	N
T/D	0.3036	likely_benign	0.2709	benign	0.418	Stabilizing	0.007	N	0.259	neutral	None	None	None	None	N
T/E	0.2718	likely_benign	0.2307	benign	0.363	Stabilizing	0.329	N	0.399	neutral	None	None	None	None	N
T/F	0.3214	likely_benign	0.3197	benign	-0.829	Destabilizing	0.981	D	0.49	neutral	None	None	None	None	N
T/G	0.2369	likely_benign	0.2331	benign	-0.611	Destabilizing	0.495	N	0.475	neutral	None	None	None	None	N
T/H	0.2618	likely_benign	0.2658	benign	-0.926	Destabilizing	0.944	D	0.489	neutral	None	None	None	None	N
T/I	0.2345	likely_benign	0.227	benign	-0.126	Destabilizing	0.927	D	0.447	neutral	N	0.513606992	None	None	N
T/K	0.1692	likely_benign	0.1523	benign	-0.337	Destabilizing	0.007	N	0.271	neutral	None	None	None	None	N
T/L	0.1158	likely_benign	0.1139	benign	-0.126	Destabilizing	0.704	D	0.393	neutral	None	None	None	None	N
T/M	0.1039	likely_benign	0.0986	benign	0.035	Stabilizing	0.981	D	0.453	neutral	None	None	None	None	N
T/N	0.1	likely_benign	0.0964	benign	-0.167	Destabilizing	0.023	N	0.191	neutral	N	0.44382162	None	None	N
T/P	0.1158	likely_benign	0.1107	benign	-0.202	Destabilizing	0.784	D	0.441	neutral	N	0.491788925	None	None	N
T/Q	0.1794	likely_benign	0.1706	benign	-0.355	Destabilizing	0.085	N	0.281	neutral	None	None	None	None	N
T/R	0.1577	likely_benign	0.1497	benign	-0.138	Destabilizing	0.543	D	0.399	neutral	None	None	None	None	N
T/S	0.1135	likely_benign	0.1053	benign	-0.438	Destabilizing	0.029	N	0.189	neutral	N	0.449382155	None	None	N
T/V	0.1817	likely_benign	0.1759	benign	-0.202	Destabilizing	0.828	D	0.261	neutral	None	None	None	None	N
T/W	0.5941	likely_pathogenic	0.6154	pathogenic	-0.805	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	N
T/Y	0.2921	likely_benign	0.3292	benign	-0.529	Destabilizing	0.981	D	0.489	neutral	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.