TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14845	44758;44759;44760	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
N2AB	13204	39835;39836;39837	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
N2A	12277	37054;37055;37056	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
N2B	5780	17563;17564;17565	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
Novex-1	5905	17938;17939;17940	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
Novex-2	5972	18139;18140;18141	chr2:178625288;178625287;178625286	chr2:179490015;179490014;179490013
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-99
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.621
• 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
N/H	None	None	0.303	N	0.445	0.118	0.0666544352282	gnomAD-4.0.0	6.8765E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.17503E-05	0
N/S	None	None	0.002	N	0.145	0.101	0.0401082797425	gnomAD-4.0.0	3.22103E-06	None	None	None	None	N	None	0	0	None	0	5.61388E-05	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
N/A	0.2265	likely_benign	0.1749	benign	-0.809	Destabilizing	0.016	N	0.408	neutral	None	None	None	None	N
N/C	0.3263	likely_benign	0.2445	benign	0.101	Stabilizing	0.869	D	0.532	neutral	None	None	None	None	N
N/D	0.2026	likely_benign	0.1637	benign	-0.296	Destabilizing	0.025	N	0.338	neutral	N	0.331526442	None	None	N
N/E	0.3302	likely_benign	0.2624	benign	-0.251	Destabilizing	0.016	N	0.329	neutral	None	None	None	None	N
N/F	0.4769	ambiguous	0.3804	ambiguous	-0.768	Destabilizing	0.637	D	0.541	neutral	None	None	None	None	N
N/G	0.3852	ambiguous	0.3041	benign	-1.099	Destabilizing	0.032	N	0.319	neutral	None	None	None	None	N
N/H	0.0838	likely_benign	0.0659	benign	-0.925	Destabilizing	0.303	N	0.445	neutral	N	0.345569488	None	None	N
N/I	0.18	likely_benign	0.1511	benign	-0.098	Destabilizing	0.303	N	0.562	neutral	N	0.334209355	None	None	N
N/K	0.1414	likely_benign	0.116	benign	-0.195	Destabilizing	None	N	0.141	neutral	N	0.344705782	None	None	N
N/L	0.1794	likely_benign	0.1463	benign	-0.098	Destabilizing	0.075	N	0.479	neutral	None	None	None	None	N
N/M	0.2667	likely_benign	0.2222	benign	0.399	Stabilizing	0.637	D	0.531	neutral	None	None	None	None	N
N/P	0.7693	likely_pathogenic	0.7255	pathogenic	-0.306	Destabilizing	0.366	N	0.534	neutral	None	None	None	None	N
N/Q	0.2211	likely_benign	0.172	benign	-0.785	Destabilizing	0.003	N	0.197	neutral	None	None	None	None	N
N/R	0.1818	likely_benign	0.1344	benign	-0.15	Destabilizing	0.039	N	0.319	neutral	None	None	None	None	N
N/S	0.0856	likely_benign	0.0777	benign	-0.697	Destabilizing	0.002	N	0.145	neutral	N	0.34373754	None	None	N
N/T	0.1121	likely_benign	0.0963	benign	-0.47	Destabilizing	0.03	N	0.327	neutral	N	0.34852312	None	None	N
N/V	0.1804	likely_benign	0.1444	benign	-0.306	Destabilizing	0.075	N	0.528	neutral	None	None	None	None	N
N/W	0.7527	likely_pathogenic	0.6321	pathogenic	-0.556	Destabilizing	0.869	D	0.581	neutral	None	None	None	None	N
N/Y	0.1464	likely_benign	0.1151	benign	-0.361	Destabilizing	0.303	N	0.543	neutral	N	0.327097007	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.