TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10038	30337;30338;30339	chr2:178704258;178704257;178704256	chr2:179568985;179568984;179568983
N2AB	9721	29386;29387;29388	chr2:178704258;178704257;178704256	chr2:179568985;179568984;179568983
N2A	8794	26605;26606;26607	chr2:178704258;178704257;178704256	chr2:179568985;179568984;179568983
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-85
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.4998
• 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
V/E	rs1490418231	-1.074	0.961	None	0.751	0.338	0.560491779295	gnomAD-2.1.1	8.02E-06	None	None	None	None	N	None	0	0	None	0	1.11272E-04	None	0	None	0	0	0
V/L	None	None	0.91	None	0.617	0.211	0.489589578638	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85753E-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
V/A	0.3438	ambiguous	0.3811	ambiguous	-1.136	Destabilizing	0.122	N	0.319	neutral	None	None	None	None	N
V/C	0.9549	likely_pathogenic	0.9677	pathogenic	-0.689	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
V/D	0.7994	likely_pathogenic	0.8002	pathogenic	-1.347	Destabilizing	0.996	D	0.787	deleterious	None	None	None	None	N
V/E	0.6125	likely_pathogenic	0.6138	pathogenic	-1.445	Destabilizing	0.961	D	0.751	deleterious	None	None	None	None	N
V/F	0.5373	ambiguous	0.5337	ambiguous	-1.328	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
V/G	0.5343	ambiguous	0.5616	ambiguous	-1.33	Destabilizing	0.925	D	0.751	deleterious	None	None	None	None	N
V/H	0.9249	likely_pathogenic	0.9292	pathogenic	-0.967	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/I	0.1185	likely_benign	0.1251	benign	-0.739	Destabilizing	0.985	D	0.583	neutral	None	None	None	None	N
V/K	0.6998	likely_pathogenic	0.6918	pathogenic	-0.838	Destabilizing	0.503	D	0.515	neutral	None	None	None	None	N
V/L	0.626	likely_pathogenic	0.6447	pathogenic	-0.739	Destabilizing	0.91	D	0.617	neutral	None	None	None	None	N
V/M	0.3289	likely_benign	0.3535	ambiguous	-0.394	Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
V/N	0.674	likely_pathogenic	0.6951	pathogenic	-0.536	Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
V/P	0.9513	likely_pathogenic	0.9586	pathogenic	-0.838	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
V/Q	0.6992	likely_pathogenic	0.7025	pathogenic	-0.879	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
V/R	0.6633	likely_pathogenic	0.6553	pathogenic	-0.239	Destabilizing	0.983	D	0.779	deleterious	None	None	None	None	N
V/S	0.509	ambiguous	0.5307	ambiguous	-0.875	Destabilizing	0.942	D	0.75	deleterious	None	None	None	None	N
V/T	0.2613	likely_benign	0.3	benign	-0.887	Destabilizing	0.97	D	0.611	neutral	None	None	None	None	N
V/W	0.9666	likely_pathogenic	0.9642	pathogenic	-1.419	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
V/Y	0.8947	likely_pathogenic	0.8934	pathogenic	-1.12	Destabilizing	0.999	D	0.721	prob.delet.	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.