TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5934	18025;18026;18027	chr2:178730733;178730732;178730731	chr2:179595460;179595459;179595458
N2AB	5617	17074;17075;17076	chr2:178730733;178730732;178730731	chr2:179595460;179595459;179595458
N2A	4690	14293;14294;14295	chr2:178730733;178730732;178730731	chr2:179595460;179595459;179595458
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-43
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2487
• 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
S/Y	None	None	1.0	N	0.771	0.432	0.594113984522	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1318	likely_benign	0.1334	benign	-0.759	Destabilizing	0.997	D	0.471	neutral	N	0.490110404	None	None	N
S/C	0.269	likely_benign	0.2652	benign	-0.423	Destabilizing	1.0	D	0.735	prob.delet.	N	0.488915337	None	None	N
S/D	0.645	likely_pathogenic	0.6708	pathogenic	0.76	Stabilizing	0.999	D	0.653	neutral	None	None	None	None	N
S/E	0.778	likely_pathogenic	0.8014	pathogenic	0.735	Stabilizing	0.999	D	0.636	neutral	None	None	None	None	N
S/F	0.4619	ambiguous	0.4699	ambiguous	-1.03	Destabilizing	1.0	D	0.761	deleterious	N	0.500271643	None	None	N
S/G	0.1889	likely_benign	0.2043	benign	-0.957	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	N
S/H	0.5612	ambiguous	0.5658	pathogenic	-1.28	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/I	0.4673	ambiguous	0.4801	ambiguous	-0.343	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/K	0.8757	likely_pathogenic	0.8885	pathogenic	-0.253	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
S/L	0.2229	likely_benign	0.2244	benign	-0.343	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
S/M	0.3899	ambiguous	0.3963	ambiguous	-0.183	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/N	0.2792	likely_benign	0.3085	benign	-0.087	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
S/P	0.8706	likely_pathogenic	0.8965	pathogenic	-0.451	Destabilizing	1.0	D	0.737	prob.delet.	N	0.488408358	None	None	N
S/Q	0.7054	likely_pathogenic	0.7165	pathogenic	-0.246	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
S/R	0.8179	likely_pathogenic	0.8278	pathogenic	-0.194	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
S/T	0.1479	likely_benign	0.151	benign	-0.296	Destabilizing	0.999	D	0.47	neutral	N	0.510947036	None	None	N
S/V	0.4158	ambiguous	0.4251	ambiguous	-0.451	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
S/W	0.6563	likely_pathogenic	0.6513	pathogenic	-0.92	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
S/Y	0.3449	ambiguous	0.346	ambiguous	-0.67	Destabilizing	1.0	D	0.771	deleterious	N	0.461340881	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.