TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8702	26329;26330;26331	chr2:178715082;178715081;178715080	chr2:179579809;179579808;179579807
N2AB	8385	25378;25379;25380	chr2:178715082;178715081;178715080	chr2:179579809;179579808;179579807
N2A	7458	22597;22598;22599	chr2:178715082;178715081;178715080	chr2:179579809;179579808;179579807
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: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-72
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0872
• 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/V	rs1560608555	None	0.011	D	0.265	0.349	0.643072836008	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs1560608555	None	0.011	D	0.265	0.349	0.643072836008	gnomAD-4.0.0	3.18287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71772E-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
I/A	0.92	likely_pathogenic	0.9359	pathogenic	-3.151	Highly Destabilizing	0.993	D	0.698	prob.neutral	None	None	None	None	N
I/C	0.9098	likely_pathogenic	0.9339	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
I/D	0.9959	likely_pathogenic	0.997	pathogenic	-3.843	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/E	0.9928	likely_pathogenic	0.9944	pathogenic	-3.519	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/F	0.3413	ambiguous	0.4443	ambiguous	-1.868	Destabilizing	0.999	D	0.705	prob.neutral	D	0.558791299	None	None	N
I/G	0.9851	likely_pathogenic	0.9884	pathogenic	-3.757	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/H	0.9597	likely_pathogenic	0.9723	pathogenic	-3.365	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/K	0.9753	likely_pathogenic	0.9819	pathogenic	-2.529	Highly Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
I/L	0.1998	likely_benign	0.2364	benign	-1.311	Destabilizing	0.083	N	0.402	neutral	D	0.543459508	None	None	N
I/M	0.2712	likely_benign	0.3192	benign	-1.468	Destabilizing	0.967	D	0.677	prob.neutral	D	0.624090287	None	None	N
I/N	0.9397	likely_pathogenic	0.9495	pathogenic	-3.246	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.651041028	None	None	N
I/P	0.993	likely_pathogenic	0.9952	pathogenic	-1.918	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
I/Q	0.9768	likely_pathogenic	0.983	pathogenic	-2.897	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
I/R	0.9594	likely_pathogenic	0.9696	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/S	0.9283	likely_pathogenic	0.9403	pathogenic	-3.799	Highly Destabilizing	0.999	D	0.827	deleterious	D	0.635021667	None	None	N
I/T	0.9271	likely_pathogenic	0.9363	pathogenic	-3.318	Highly Destabilizing	0.984	D	0.76	deleterious	D	0.65063742	None	None	N
I/V	0.1122	likely_benign	0.1139	benign	-1.918	Destabilizing	0.011	N	0.265	neutral	D	0.543398788	None	None	N
I/W	0.9691	likely_pathogenic	0.9825	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/Y	0.8584	likely_pathogenic	0.8995	pathogenic	-2.146	Highly Destabilizing	0.989	D	0.768	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.