TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17930	54013;54014;54015	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
N2AB	16289	49090;49091;49092	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
N2A	15362	46309;46310;46311	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
N2B	8865	26818;26819;26820	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
Novex-1	8990	27193;27194;27195	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
Novex-2	9057	27394;27395;27396	chr2:178605507;178605506;178605505	chr2:179470234;179470233;179470232
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-18
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.7691
• 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
H/Q	rs1211145414	0.566	0.917	N	0.415	0.169	0.193865811164	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
H/Q	rs1211145414	0.566	0.917	N	0.415	0.169	0.193865811164	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/Q	rs1211145414	0.566	0.917	N	0.415	0.169	0.193865811164	gnomAD-4.0.0	3.72164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08944E-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
H/A	0.4103	ambiguous	0.3031	benign	0.327	Stabilizing	0.004	N	0.242	neutral	None	None	None	None	N
H/C	0.2893	likely_benign	0.2329	benign	0.883	Stabilizing	0.981	D	0.535	neutral	None	None	None	None	N
H/D	0.308	likely_benign	0.2479	benign	-0.131	Destabilizing	0.784	D	0.51	neutral	N	0.357210207	None	None	N
H/E	0.4222	ambiguous	0.3318	benign	-0.094	Destabilizing	0.665	D	0.351	neutral	None	None	None	None	N
H/F	0.2849	likely_benign	0.2394	benign	1.115	Stabilizing	0.003	N	0.201	neutral	None	None	None	None	N
H/G	0.2731	likely_benign	0.2163	benign	0.022	Stabilizing	0.495	N	0.492	neutral	None	None	None	None	N
H/I	0.5528	ambiguous	0.4493	ambiguous	1.116	Stabilizing	0.329	N	0.538	neutral	None	None	None	None	N
H/K	0.3099	likely_benign	0.2441	benign	0.246	Stabilizing	0.665	D	0.483	neutral	None	None	None	None	N
H/L	0.1298	likely_benign	0.0971	benign	1.116	Stabilizing	0.001	N	0.267	neutral	N	0.408775178	None	None	N
H/M	0.4176	ambiguous	0.3269	benign	0.849	Stabilizing	0.893	D	0.535	neutral	None	None	None	None	N
H/N	0.1013	likely_benign	0.0811	benign	0.266	Stabilizing	0.917	D	0.371	neutral	N	0.343107547	None	None	N
H/P	0.5944	likely_pathogenic	0.5555	ambiguous	0.878	Stabilizing	0.784	D	0.575	neutral	N	0.496490163	None	None	N
H/Q	0.2499	likely_benign	0.1836	benign	0.399	Stabilizing	0.917	D	0.415	neutral	N	0.431419965	None	None	N
H/R	0.1912	likely_benign	0.1506	benign	-0.442	Destabilizing	0.784	D	0.354	neutral	N	0.433844194	None	None	N
H/S	0.313	likely_benign	0.2395	benign	0.449	Stabilizing	0.329	N	0.418	neutral	None	None	None	None	N
H/T	0.4032	ambiguous	0.2943	benign	0.582	Stabilizing	0.495	N	0.502	neutral	None	None	None	None	N
H/V	0.4554	ambiguous	0.3531	ambiguous	0.878	Stabilizing	0.176	N	0.474	neutral	None	None	None	None	N
H/W	0.422	ambiguous	0.4121	ambiguous	1.125	Stabilizing	0.981	D	0.519	neutral	None	None	None	None	N
H/Y	0.1186	likely_benign	0.1034	benign	1.367	Stabilizing	0.27	N	0.376	neutral	N	0.408543105	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.