TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22495	67708;67709;67710	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
N2AB	20854	62785;62786;62787	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
N2A	19927	60004;60005;60006	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
N2B	13430	40513;40514;40515	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
Novex-1	13555	40888;40889;40890	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
Novex-2	13622	41089;41090;41091	chr2:178579714;178579713;178579712	chr2:179444441;179444440;179444439
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-51
• Domain position: 45
• Structural Position: 63
• Q(SASA): 1.0578
• 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/S	None	None	0.425	N	0.321	0.136	0.110078149338	gnomAD-4.0.0	2.05318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69895E-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
N/A	0.2479	likely_benign	0.2062	benign	-0.256	Destabilizing	0.495	N	0.374	neutral	None	None	None	None	N
N/C	0.3577	ambiguous	0.2995	benign	0.347	Stabilizing	0.995	D	0.275	neutral	None	None	None	None	N
N/D	0.1187	likely_benign	0.1096	benign	0.244	Stabilizing	0.001	N	0.099	neutral	N	0.368923137	None	None	N
N/E	0.2155	likely_benign	0.1974	benign	0.219	Stabilizing	0.013	N	0.127	neutral	None	None	None	None	N
N/F	0.6942	likely_pathogenic	0.6419	pathogenic	-0.604	Destabilizing	0.944	D	0.295	neutral	None	None	None	None	N
N/G	0.1538	likely_benign	0.1415	benign	-0.437	Destabilizing	0.495	N	0.328	neutral	None	None	None	None	N
N/H	0.1624	likely_benign	0.1417	benign	-0.438	Destabilizing	0.006	N	0.295	neutral	N	0.467241905	None	None	N
N/I	0.3711	ambiguous	0.326	benign	0.136	Stabilizing	0.927	D	0.323	neutral	N	0.45823842	None	None	N
N/K	0.1711	likely_benign	0.1466	benign	0.093	Stabilizing	0.27	N	0.349	neutral	N	0.428299515	None	None	N
N/L	0.3472	ambiguous	0.3022	benign	0.136	Stabilizing	0.704	D	0.317	neutral	None	None	None	None	N
N/M	0.3747	ambiguous	0.3322	benign	0.325	Stabilizing	0.981	D	0.307	neutral	None	None	None	None	N
N/P	0.746	likely_pathogenic	0.679	pathogenic	0.032	Stabilizing	0.828	D	0.331	neutral	None	None	None	None	N
N/Q	0.2398	likely_benign	0.2054	benign	-0.25	Destabilizing	0.085	N	0.243	neutral	None	None	None	None	N
N/R	0.2551	likely_benign	0.2198	benign	0.112	Stabilizing	0.704	D	0.319	neutral	None	None	None	None	N
N/S	0.1053	likely_benign	0.0956	benign	-0.095	Destabilizing	0.425	N	0.321	neutral	N	0.412423198	None	None	N
N/T	0.174	likely_benign	0.1492	benign	0.025	Stabilizing	0.6	D	0.306	neutral	N	0.430915745	None	None	N
N/V	0.3565	ambiguous	0.3093	benign	0.032	Stabilizing	0.828	D	0.313	neutral	None	None	None	None	N
N/W	0.7897	likely_pathogenic	0.7384	pathogenic	-0.624	Destabilizing	0.995	D	0.265	neutral	None	None	None	None	N
N/Y	0.2099	likely_benign	0.1919	benign	-0.346	Destabilizing	0.863	D	0.329	neutral	N	0.464260315	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.