TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29674	89245;89246;89247	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
N2AB	28033	84322;84323;84324	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
N2A	27106	81541;81542;81543	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
N2B	20609	62050;62051;62052	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
Novex-1	20734	62425;62426;62427	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
Novex-2	20801	62626;62627;62628	chr2:178554091;178554090;178554089	chr2:179418818;179418817;179418816
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-104
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2884
• 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
D/N	None	None	0.989	N	0.509	0.342	0.388970301349	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	2.28634E-05	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
D/A	0.5183	ambiguous	0.6695	pathogenic	-0.652	Destabilizing	0.978	D	0.557	neutral	N	0.505512291	None	None	N
D/C	0.7056	likely_pathogenic	0.7904	pathogenic	-0.251	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/E	0.1985	likely_benign	0.2576	benign	-0.614	Destabilizing	0.198	N	0.196	neutral	N	0.371984872	None	None	N
D/F	0.8865	likely_pathogenic	0.9444	pathogenic	-0.057	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
D/G	0.4751	ambiguous	0.6528	pathogenic	-1.058	Destabilizing	0.989	D	0.535	neutral	N	0.506205725	None	None	N
D/H	0.5941	likely_pathogenic	0.7293	pathogenic	-0.357	Destabilizing	1.0	D	0.661	neutral	N	0.467013918	None	None	N
D/I	0.7429	likely_pathogenic	0.8475	pathogenic	0.445	Stabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
D/K	0.8132	likely_pathogenic	0.8939	pathogenic	-0.41	Destabilizing	0.983	D	0.488	neutral	None	None	None	None	N
D/L	0.7212	likely_pathogenic	0.8181	pathogenic	0.445	Stabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
D/M	0.8428	likely_pathogenic	0.915	pathogenic	0.979	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/N	0.2138	likely_benign	0.3108	benign	-0.961	Destabilizing	0.989	D	0.509	neutral	N	0.51063011	None	None	N
D/P	0.9598	likely_pathogenic	0.9806	pathogenic	0.105	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	N
D/Q	0.5919	likely_pathogenic	0.7085	pathogenic	-0.773	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	N
D/R	0.8242	likely_pathogenic	0.8963	pathogenic	-0.251	Destabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
D/S	0.3227	likely_benign	0.4615	ambiguous	-1.324	Destabilizing	0.983	D	0.444	neutral	None	None	None	None	N
D/T	0.5845	likely_pathogenic	0.7426	pathogenic	-0.969	Destabilizing	0.998	D	0.556	neutral	None	None	None	None	N
D/V	0.5585	ambiguous	0.6942	pathogenic	0.105	Stabilizing	0.997	D	0.718	prob.delet.	N	0.511323543	None	None	N
D/W	0.961	likely_pathogenic	0.9785	pathogenic	0.169	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
D/Y	0.5635	ambiguous	0.713	pathogenic	0.222	Stabilizing	0.999	D	0.737	prob.delet.	N	0.502096793	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.