TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19114	57565;57566;57567	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
N2AB	17473	52642;52643;52644	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
N2A	16546	49861;49862;49863	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
N2B	10049	30370;30371;30372	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
Novex-1	10174	30745;30746;30747	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
Novex-2	10241	30946;30947;30948	chr2:178597742;178597741;178597740	chr2:179462469;179462468;179462467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-117
• Domain position: 20
• Structural Position: 33
• Q(SASA): 0.1409
• 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/T	rs2052103828	None	1.0	N	0.847	0.429	0.385417323374	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	1.26695E-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
A/C	0.6773	likely_pathogenic	0.725	pathogenic	-0.475	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/D	0.9962	likely_pathogenic	0.9977	pathogenic	0.095	Stabilizing	1.0	D	0.881	deleterious	N	0.486268765	None	None	N
A/E	0.9954	likely_pathogenic	0.9971	pathogenic	0.169	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/F	0.9363	likely_pathogenic	0.9613	pathogenic	-0.375	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
A/G	0.2774	likely_benign	0.3291	benign	-0.812	Destabilizing	1.0	D	0.687	prob.neutral	N	0.46791102	None	None	N
A/H	0.9941	likely_pathogenic	0.9964	pathogenic	-0.895	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
A/I	0.7742	likely_pathogenic	0.8493	pathogenic	0.39	Stabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9989	pathogenic	-0.338	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/L	0.7218	likely_pathogenic	0.7799	pathogenic	0.39	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/M	0.8392	likely_pathogenic	0.8879	pathogenic	0.132	Stabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/N	0.9815	likely_pathogenic	0.9889	pathogenic	-0.266	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
A/P	0.9882	likely_pathogenic	0.9942	pathogenic	0.152	Stabilizing	1.0	D	0.865	deleterious	N	0.486268765	None	None	N
A/Q	0.9868	likely_pathogenic	0.9905	pathogenic	-0.179	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/R	0.9932	likely_pathogenic	0.9955	pathogenic	-0.401	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/S	0.2933	likely_benign	0.3469	ambiguous	-0.838	Destabilizing	1.0	D	0.677	prob.neutral	N	0.462884591	None	None	N
A/T	0.3799	ambiguous	0.4878	ambiguous	-0.618	Destabilizing	1.0	D	0.847	deleterious	N	0.474151991	None	None	N
A/V	0.4514	ambiguous	0.5594	ambiguous	0.152	Stabilizing	1.0	D	0.762	deleterious	N	0.457803197	None	None	N
A/W	0.9966	likely_pathogenic	0.9982	pathogenic	-0.809	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
A/Y	0.9801	likely_pathogenic	0.9879	pathogenic	-0.271	Destabilizing	1.0	D	0.91	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.