TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8972	27139;27140;27141	chr2:178713220;178713219;178713218	chr2:179577947;179577946;179577945
N2AB	8655	26188;26189;26190	chr2:178713220;178713219;178713218	chr2:179577947;179577946;179577945
N2A	7728	23407;23408;23409	chr2:178713220;178713219;178713218	chr2:179577947;179577946;179577945
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-75
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2144
• 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
Y/C	None	None	1.0	N	0.749	0.484	0.727831686896	gnomAD-4.0.0	3.18357E-06	None	None	None	None	N	None	0	4.57708E-05	None	0	0	None	0	0	0	0	0
Y/H	None	None	0.265	N	0.394	0.305	0.353125101423	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-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
Y/A	0.8928	likely_pathogenic	0.921	pathogenic	-2.705	Highly Destabilizing	0.993	D	0.618	neutral	None	None	None	None	N
Y/C	0.3555	ambiguous	0.4236	ambiguous	-2.065	Highly Destabilizing	1.0	D	0.749	deleterious	N	0.499129911	None	None	N
Y/D	0.8932	likely_pathogenic	0.9246	pathogenic	-1.901	Destabilizing	0.997	D	0.767	deleterious	N	0.49963689	None	None	N
Y/E	0.9424	likely_pathogenic	0.9597	pathogenic	-1.739	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
Y/F	0.134	likely_benign	0.1429	benign	-1.229	Destabilizing	0.135	N	0.369	neutral	N	0.438186513	None	None	N
Y/G	0.8488	likely_pathogenic	0.877	pathogenic	-3.106	Highly Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
Y/H	0.4442	ambiguous	0.4893	ambiguous	-1.697	Destabilizing	0.265	N	0.394	neutral	N	0.503507428	None	None	N
Y/I	0.6883	likely_pathogenic	0.7369	pathogenic	-1.428	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
Y/K	0.9131	likely_pathogenic	0.9404	pathogenic	-1.857	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
Y/L	0.6981	likely_pathogenic	0.7462	pathogenic	-1.428	Destabilizing	0.971	D	0.537	neutral	None	None	None	None	N
Y/M	0.829	likely_pathogenic	0.8646	pathogenic	-1.368	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
Y/N	0.589	likely_pathogenic	0.6649	pathogenic	-2.408	Highly Destabilizing	0.994	D	0.725	prob.delet.	N	0.502016747	None	None	N
Y/P	0.9857	likely_pathogenic	0.9886	pathogenic	-1.858	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
Y/Q	0.8618	likely_pathogenic	0.9004	pathogenic	-2.199	Highly Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
Y/R	0.8098	likely_pathogenic	0.8601	pathogenic	-1.568	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
Y/S	0.7256	likely_pathogenic	0.7904	pathogenic	-3.015	Highly Destabilizing	0.997	D	0.657	neutral	N	0.487266627	None	None	N
Y/T	0.8407	likely_pathogenic	0.8923	pathogenic	-2.729	Highly Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
Y/V	0.6369	likely_pathogenic	0.6928	pathogenic	-1.858	Destabilizing	0.985	D	0.61	neutral	None	None	None	None	N
Y/W	0.5681	likely_pathogenic	0.5984	pathogenic	-0.677	Destabilizing	1.0	D	0.613	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.