TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4947	15064;15065;15066	chr2:178735607;178735606;178735605	chr2:179600334;179600333;179600332
N2AB	4630	14113;14114;14115	chr2:178735607;178735606;178735605	chr2:179600334;179600333;179600332
N2A	3703	11332;11333;11334	chr2:178735607;178735606;178735605	chr2:179600334;179600333;179600332
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: 60
• Structural Position: 140
• Q(SASA): 0.112
• 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/T	None	None	1.0	D	0.823	0.833	0.860303665231	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.9273	likely_pathogenic	0.9442	pathogenic	-3.003	Highly Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
I/C	0.9372	likely_pathogenic	0.9497	pathogenic	-2.347	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
I/D	0.984	likely_pathogenic	0.9876	pathogenic	-3.706	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/E	0.9778	likely_pathogenic	0.9822	pathogenic	-3.468	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/F	0.2562	likely_benign	0.2702	benign	-1.796	Destabilizing	1.0	D	0.817	deleterious	D	0.533297191	None	None	N
I/G	0.9769	likely_pathogenic	0.9823	pathogenic	-3.551	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/H	0.9333	likely_pathogenic	0.9431	pathogenic	-3.003	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/K	0.9301	likely_pathogenic	0.9408	pathogenic	-2.637	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/L	0.1762	likely_benign	0.1894	benign	-1.392	Destabilizing	0.993	D	0.423	neutral	N	0.485721347	None	None	N
I/M	0.1583	likely_benign	0.1771	benign	-1.34	Destabilizing	1.0	D	0.758	deleterious	D	0.537082221	None	None	N
I/N	0.8046	likely_pathogenic	0.8273	pathogenic	-3.045	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.595839816	None	None	N
I/P	0.9897	likely_pathogenic	0.9922	pathogenic	-1.914	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/Q	0.9469	likely_pathogenic	0.957	pathogenic	-2.896	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
I/R	0.9241	likely_pathogenic	0.9371	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
I/S	0.892	likely_pathogenic	0.9095	pathogenic	-3.672	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.686774341	None	None	N
I/T	0.934	likely_pathogenic	0.9481	pathogenic	-3.299	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.608651657	None	None	N
I/V	0.2143	likely_benign	0.2291	benign	-1.914	Destabilizing	0.993	D	0.403	neutral	N	0.430576631	None	None	N
I/W	0.9369	likely_pathogenic	0.9427	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
I/Y	0.7432	likely_pathogenic	0.7532	pathogenic	-2.045	Highly Destabilizing	1.0	D	0.829	deleterious	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.