TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5018	15277;15278;15279	chr2:178734872;178734871;178734870	chr2:179599599;179599598;179599597
N2AB	4701	14326;14327;14328	chr2:178734872;178734871;178734870	chr2:179599599;179599598;179599597
N2A	3774	11545;11546;11547	chr2:178734872;178734871;178734870	chr2:179599599;179599598;179599597
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-33
• Domain position: 38
• Structural Position: 51
• Q(SASA): 0.4681
• 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	0.201	D	0.437	0.262	0.149567049428	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	1.90042E-04	0	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
N/A	0.6297	likely_pathogenic	0.6547	pathogenic	-0.718	Destabilizing	0.399	N	0.543	neutral	None	None	None	None	N
N/C	0.6884	likely_pathogenic	0.7409	pathogenic	0.212	Stabilizing	0.982	D	0.669	neutral	None	None	None	None	N
N/D	0.1466	likely_benign	0.1382	benign	0.112	Stabilizing	0.001	N	0.233	neutral	N	0.44576975	None	None	N
N/E	0.6153	likely_pathogenic	0.6241	pathogenic	0.11	Stabilizing	0.25	N	0.433	neutral	None	None	None	None	N
N/F	0.8928	likely_pathogenic	0.9058	pathogenic	-0.941	Destabilizing	0.982	D	0.667	neutral	None	None	None	None	N
N/G	0.3881	ambiguous	0.4041	ambiguous	-0.937	Destabilizing	0.399	N	0.423	neutral	None	None	None	None	N
N/H	0.3017	likely_benign	0.3166	benign	-0.893	Destabilizing	0.781	D	0.53	neutral	D	0.61447358	None	None	N
N/I	0.8292	likely_pathogenic	0.8402	pathogenic	-0.211	Destabilizing	0.781	D	0.695	prob.neutral	D	0.615735949	None	None	N
N/K	0.6655	likely_pathogenic	0.6798	pathogenic	-0.022	Destabilizing	0.334	N	0.473	neutral	N	0.51559029	None	None	N
N/L	0.7443	likely_pathogenic	0.7477	pathogenic	-0.211	Destabilizing	0.7	D	0.683	prob.neutral	None	None	None	None	N
N/M	0.7398	likely_pathogenic	0.7547	pathogenic	0.264	Stabilizing	0.982	D	0.62	neutral	None	None	None	None	N
N/P	0.9878	likely_pathogenic	0.987	pathogenic	-0.353	Destabilizing	0.826	D	0.626	neutral	None	None	None	None	N
N/Q	0.6031	likely_pathogenic	0.6095	pathogenic	-0.525	Destabilizing	0.7	D	0.531	neutral	None	None	None	None	N
N/R	0.7046	likely_pathogenic	0.7164	pathogenic	0.011	Stabilizing	0.7	D	0.537	neutral	None	None	None	None	N
N/S	0.215	likely_benign	0.2148	benign	-0.393	Destabilizing	0.201	N	0.437	neutral	D	0.551786342	None	None	N
N/T	0.6268	likely_pathogenic	0.6267	pathogenic	-0.225	Destabilizing	0.334	N	0.468	neutral	D	0.588128978	None	None	N
N/V	0.8128	likely_pathogenic	0.825	pathogenic	-0.353	Destabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	N
N/W	0.938	likely_pathogenic	0.9441	pathogenic	-0.807	Destabilizing	0.982	D	0.663	neutral	None	None	None	None	N
N/Y	0.4125	ambiguous	0.4383	ambiguous	-0.592	Destabilizing	0.916	D	0.615	neutral	D	0.615735949	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.