TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4891	14896;14897;14898	chr2:178735775;178735774;178735773	chr2:179600502;179600501;179600500
N2AB	4574	13945;13946;13947	chr2:178735775;178735774;178735773	chr2:179600502;179600501;179600500
N2A	3647	11164;11165;11166	chr2:178735775;178735774;178735773	chr2:179600502;179600501;179600500
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-32
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.8
• 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
I/L	rs1304712343	None	0.267	N	0.173	0.072	0.419835214384	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/L	rs1304712343	None	0.267	N	0.173	0.072	0.419835214384	gnomAD-4.0.0	6.56996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46972E-05	0	0
I/S	None	None	0.136	N	0.183	0.154	0.51081628273	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.4803	ambiguous	0.392	ambiguous	-1.13	Destabilizing	0.525	D	0.275	neutral	None	None	None	None	N
I/C	0.7197	likely_pathogenic	0.6307	pathogenic	-0.707	Destabilizing	0.998	D	0.279	neutral	None	None	None	None	N
I/D	0.767	likely_pathogenic	0.688	pathogenic	-0.509	Destabilizing	0.842	D	0.423	neutral	None	None	None	None	N
I/E	0.547	ambiguous	0.4596	ambiguous	-0.546	Destabilizing	0.842	D	0.398	neutral	None	None	None	None	N
I/F	0.2092	likely_benign	0.1673	benign	-0.778	Destabilizing	0.934	D	0.294	neutral	N	0.480711742	None	None	N
I/G	0.7079	likely_pathogenic	0.6032	pathogenic	-1.385	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	N
I/H	0.5091	ambiguous	0.4131	ambiguous	-0.477	Destabilizing	0.998	D	0.316	neutral	None	None	None	None	N
I/K	0.3365	likely_benign	0.2664	benign	-0.723	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
I/L	0.1212	likely_benign	0.1032	benign	-0.54	Destabilizing	0.267	N	0.173	neutral	N	0.349013657	None	None	N
I/M	0.1343	likely_benign	0.1145	benign	-0.474	Destabilizing	0.966	D	0.289	neutral	N	0.446047051	None	None	N
I/N	0.3464	ambiguous	0.2849	benign	-0.564	Destabilizing	0.934	D	0.409	neutral	N	0.473039118	None	None	N
I/P	0.7997	likely_pathogenic	0.7712	pathogenic	-0.704	Destabilizing	0.974	D	0.395	neutral	None	None	None	None	N
I/Q	0.375	ambiguous	0.2972	benign	-0.763	Destabilizing	0.974	D	0.371	neutral	None	None	None	None	N
I/R	0.237	likely_benign	0.191	benign	-0.092	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	N
I/S	0.3339	likely_benign	0.2797	benign	-1.11	Destabilizing	0.136	N	0.183	neutral	N	0.449635113	None	None	N
I/T	0.2566	likely_benign	0.2109	benign	-1.036	Destabilizing	0.051	N	0.153	neutral	N	0.438836652	None	None	N
I/V	0.0973	likely_benign	0.0844	benign	-0.704	Destabilizing	0.005	N	0.138	neutral	N	0.426081823	None	None	N
I/W	0.7368	likely_pathogenic	0.641	pathogenic	-0.808	Destabilizing	0.998	D	0.367	neutral	None	None	None	None	N
I/Y	0.5618	ambiguous	0.4777	ambiguous	-0.587	Destabilizing	0.974	D	0.319	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.