TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34420	103483;103484;103485	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
N2AB	32779	98560;98561;98562	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
N2A	31852	95779;95780;95781	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
N2B	25355	76288;76289;76290	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
Novex-1	25480	76663;76664;76665	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
Novex-2	25547	76864;76865;76866	chr2:178533357;178533356;178533355	chr2:179398084;179398083;179398082
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-162
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.0674
• 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
A/V	None	None	0.122	N	0.315	0.295	0.511848488485	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
A/C	0.6927	likely_pathogenic	0.6676	pathogenic	-0.84	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
A/D	0.9714	likely_pathogenic	0.9657	pathogenic	-2.658	Highly Destabilizing	0.994	D	0.712	prob.delet.	N	0.489556696	None	None	N
A/E	0.9063	likely_pathogenic	0.8916	pathogenic	-2.378	Highly Destabilizing	0.996	D	0.728	prob.delet.	None	None	None	None	N
A/F	0.7984	likely_pathogenic	0.7591	pathogenic	-0.659	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
A/G	0.4829	ambiguous	0.4528	ambiguous	-1.634	Destabilizing	0.98	D	0.659	neutral	N	0.466834552	None	None	N
A/H	0.9056	likely_pathogenic	0.8945	pathogenic	-2.232	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/I	0.6938	likely_pathogenic	0.6557	pathogenic	0.327	Stabilizing	0.942	D	0.7	prob.neutral	None	None	None	None	N
A/K	0.9422	likely_pathogenic	0.9351	pathogenic	-1.117	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
A/L	0.6243	likely_pathogenic	0.5978	pathogenic	0.327	Stabilizing	0.871	D	0.679	prob.neutral	None	None	None	None	N
A/M	0.6645	likely_pathogenic	0.6205	pathogenic	0.037	Stabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
A/N	0.8889	likely_pathogenic	0.8649	pathogenic	-1.682	Destabilizing	0.996	D	0.736	prob.delet.	None	None	None	None	N
A/P	0.9935	likely_pathogenic	0.9925	pathogenic	-0.119	Destabilizing	0.998	D	0.705	prob.neutral	D	0.530749958	None	None	N
A/Q	0.7997	likely_pathogenic	0.7841	pathogenic	-1.336	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
A/R	0.8269	likely_pathogenic	0.8288	pathogenic	-1.416	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
A/S	0.2464	likely_benign	0.2227	benign	-1.99	Destabilizing	0.925	D	0.614	neutral	N	0.393662158	None	None	N
A/T	0.3812	ambiguous	0.3373	benign	-1.583	Destabilizing	0.248	N	0.479	neutral	N	0.389792347	None	None	N
A/V	0.4458	ambiguous	0.4051	ambiguous	-0.119	Destabilizing	0.122	N	0.315	neutral	N	0.416560447	None	None	N
A/W	0.9741	likely_pathogenic	0.9712	pathogenic	-1.571	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/Y	0.8757	likely_pathogenic	0.8587	pathogenic	-0.991	Destabilizing	0.999	D	0.717	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.