TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15259	46000;46001;46002	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
N2AB	13618	41077;41078;41079	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
N2A	12691	38296;38297;38298	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
N2B	6194	18805;18806;18807	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
Novex-1	6319	19180;19181;19182	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
Novex-2	6386	19381;19382;19383	chr2:178620835;178620834;178620833	chr2:179485562;179485561;179485560
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: Ig-104
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.806
• 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/V	None	None	0.997	D	0.662	0.496	0.445210270852	gnomAD-4.0.0	4.10766E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39933E-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
D/A	0.561	ambiguous	0.4554	ambiguous	-0.151	Destabilizing	0.955	D	0.566	neutral	N	0.493246404	None	None	N
D/C	0.936	likely_pathogenic	0.8823	pathogenic	-0.243	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
D/E	0.4233	ambiguous	0.3374	benign	-0.2	Destabilizing	0.989	D	0.461	neutral	N	0.486545242	None	None	N
D/F	0.8802	likely_pathogenic	0.8201	pathogenic	-0.079	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
D/G	0.3162	likely_benign	0.2379	benign	-0.322	Destabilizing	0.117	N	0.381	neutral	N	0.438574827	None	None	N
D/H	0.6755	likely_pathogenic	0.572	pathogenic	0.322	Stabilizing	1.0	D	0.66	neutral	N	0.520064345	None	None	N
D/I	0.8742	likely_pathogenic	0.7969	pathogenic	0.249	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
D/K	0.8177	likely_pathogenic	0.7348	pathogenic	0.138	Stabilizing	0.998	D	0.655	neutral	None	None	None	None	N
D/L	0.8409	likely_pathogenic	0.7538	pathogenic	0.249	Stabilizing	0.998	D	0.663	neutral	None	None	None	None	N
D/M	0.935	likely_pathogenic	0.8886	pathogenic	0.095	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
D/N	0.1928	likely_benign	0.1539	benign	-0.07	Destabilizing	0.993	D	0.635	neutral	N	0.436736326	None	None	N
D/P	0.9245	likely_pathogenic	0.8914	pathogenic	0.137	Stabilizing	0.999	D	0.649	neutral	None	None	None	None	N
D/Q	0.7728	likely_pathogenic	0.6683	pathogenic	-0.036	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
D/R	0.8259	likely_pathogenic	0.7441	pathogenic	0.434	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	N
D/S	0.3823	ambiguous	0.295	benign	-0.215	Destabilizing	0.983	D	0.592	neutral	None	None	None	None	N
D/T	0.7386	likely_pathogenic	0.6299	pathogenic	-0.082	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
D/V	0.7079	likely_pathogenic	0.5986	pathogenic	0.137	Stabilizing	0.997	D	0.662	neutral	D	0.56300289	None	None	N
D/W	0.9712	likely_pathogenic	0.9542	pathogenic	0.014	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
D/Y	0.4694	ambiguous	0.3739	ambiguous	0.14	Stabilizing	1.0	D	0.677	prob.neutral	N	0.450656427	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.