TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17956	54091;54092;54093	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
N2AB	16315	49168;49169;49170	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
N2A	15388	46387;46388;46389	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
N2B	8891	26896;26897;26898	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
Novex-1	9016	27271;27272;27273	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
Novex-2	9083	27472;27473;27474	chr2:178605429;178605428;178605427	chr2:179470156;179470155;179470154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-18
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3765
• 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	None	None	0.188	N	0.215	0.119	0.415055319159	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
I/A	0.9641	likely_pathogenic	0.9561	pathogenic	-3.292	Highly Destabilizing	0.982	D	0.498	neutral	None	None	None	None	N
I/C	0.9719	likely_pathogenic	0.9593	pathogenic	-2.446	Highly Destabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	N
I/D	0.9996	likely_pathogenic	0.9994	pathogenic	-3.442	Highly Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
I/E	0.9988	likely_pathogenic	0.9985	pathogenic	-3.175	Highly Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
I/F	0.9281	likely_pathogenic	0.8993	pathogenic	-1.664	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	N
I/G	0.9974	likely_pathogenic	0.9968	pathogenic	-3.775	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
I/H	0.9989	likely_pathogenic	0.9983	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
I/K	0.998	likely_pathogenic	0.9975	pathogenic	-2.28	Highly Destabilizing	0.999	D	0.796	deleterious	N	0.4654893	None	None	N
I/L	0.5445	ambiguous	0.4893	ambiguous	-1.82	Destabilizing	0.787	D	0.447	neutral	N	0.493887002	None	None	N
I/M	0.6435	likely_pathogenic	0.5925	pathogenic	-2.132	Highly Destabilizing	0.997	D	0.655	prob.neutral	N	0.488539897	None	None	N
I/N	0.9916	likely_pathogenic	0.9869	pathogenic	-2.791	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
I/P	0.9897	likely_pathogenic	0.9812	pathogenic	-2.306	Highly Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
I/Q	0.9975	likely_pathogenic	0.9965	pathogenic	-2.524	Highly Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
I/R	0.9966	likely_pathogenic	0.9955	pathogenic	-2.126	Highly Destabilizing	0.999	D	0.809	deleterious	N	0.46574279	None	None	N
I/S	0.9837	likely_pathogenic	0.9781	pathogenic	-3.324	Highly Destabilizing	0.997	D	0.718	prob.delet.	None	None	None	None	N
I/T	0.9698	likely_pathogenic	0.9605	pathogenic	-2.932	Highly Destabilizing	0.976	D	0.613	neutral	N	0.507941229	None	None	N
I/V	0.2439	likely_benign	0.2385	benign	-2.306	Highly Destabilizing	0.188	N	0.215	neutral	N	0.441092667	None	None	N
I/W	0.9987	likely_pathogenic	0.9981	pathogenic	-1.867	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
I/Y	0.9958	likely_pathogenic	0.994	pathogenic	-1.907	Destabilizing	0.999	D	0.68	prob.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.