TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24766	74521;74522;74523	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
N2AB	23125	69598;69599;69600	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
N2A	22198	66817;66818;66819	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
N2B	15701	47326;47327;47328	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
Novex-1	15826	47701;47702;47703	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
Novex-2	15893	47902;47903;47904	chr2:178571836;178571835;178571834	chr2:179436563;179436562;179436561
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-133
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.533
• 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
S/C	None	None	0.822	N	0.499	0.289	0.427139414373	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0898	likely_benign	0.0875	benign	-0.596	Destabilizing	0.001	N	0.23	neutral	None	None	None	None	N
S/C	0.0838	likely_benign	0.0939	benign	-0.301	Destabilizing	0.822	D	0.499	neutral	N	0.520148962	None	None	N
S/D	0.2387	likely_benign	0.2855	benign	0.053	Stabilizing	0.055	N	0.347	neutral	None	None	None	None	N
S/E	0.3785	ambiguous	0.4288	ambiguous	-0.016	Destabilizing	0.104	N	0.35	neutral	None	None	None	None	N
S/F	0.218	likely_benign	0.2176	benign	-1.065	Destabilizing	0.667	D	0.566	neutral	None	None	None	None	N
S/G	0.0933	likely_benign	0.0979	benign	-0.755	Destabilizing	0.019	N	0.313	neutral	N	0.485497671	None	None	N
S/H	0.2039	likely_benign	0.2504	benign	-1.301	Destabilizing	0.497	N	0.497	neutral	None	None	None	None	N
S/I	0.0996	likely_benign	0.1128	benign	-0.296	Destabilizing	0.096	N	0.547	neutral	N	0.487036466	None	None	N
S/K	0.3832	ambiguous	0.4567	ambiguous	-0.552	Destabilizing	0.055	N	0.344	neutral	None	None	None	None	N
S/L	0.1315	likely_benign	0.1277	benign	-0.296	Destabilizing	0.055	N	0.554	neutral	None	None	None	None	N
S/M	0.1561	likely_benign	0.1641	benign	0.095	Stabilizing	0.667	D	0.496	neutral	None	None	None	None	N
S/N	0.0684	likely_benign	0.0818	benign	-0.314	Destabilizing	None	N	0.245	neutral	N	0.418560603	None	None	N
S/P	0.4112	ambiguous	0.3965	ambiguous	-0.365	Destabilizing	0.364	N	0.505	neutral	None	None	None	None	N
S/Q	0.309	likely_benign	0.3646	ambiguous	-0.573	Destabilizing	0.22	N	0.431	neutral	None	None	None	None	N
S/R	0.363	ambiguous	0.4315	ambiguous	-0.367	Destabilizing	0.175	N	0.489	neutral	N	0.503659357	None	None	N
S/T	0.0621	likely_benign	0.0629	benign	-0.418	Destabilizing	None	N	0.251	neutral	N	0.434434132	None	None	N
S/V	0.1166	likely_benign	0.1257	benign	-0.365	Destabilizing	0.002	N	0.413	neutral	None	None	None	None	N
S/W	0.3544	ambiguous	0.3826	ambiguous	-1.02	Destabilizing	0.958	D	0.56	neutral	None	None	None	None	N
S/Y	0.156	likely_benign	0.1724	benign	-0.763	Destabilizing	0.859	D	0.569	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.