TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29785	89578;89579;89580	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
N2AB	28144	84655;84656;84657	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
N2A	27217	81874;81875;81876	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
N2B	20720	62383;62384;62385	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
Novex-1	20845	62758;62759;62760	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
Novex-2	20912	62959;62960;62961	chr2:178553652;178553651;178553650	chr2:179418379;179418378;179418377
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: Fn3-105
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1498
• 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/F	None	None	0.988	N	0.626	0.286	0.589873123614	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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	0.1445	likely_benign	0.1357	benign	-0.809	Destabilizing	0.675	D	0.402	neutral	N	0.445005337	None	None	N
S/C	0.155	likely_benign	0.1499	benign	-0.576	Destabilizing	0.999	D	0.557	neutral	N	0.474183623	None	None	N
S/D	0.7539	likely_pathogenic	0.7631	pathogenic	-0.355	Destabilizing	0.969	D	0.601	neutral	None	None	None	None	N
S/E	0.851	likely_pathogenic	0.8794	pathogenic	-0.295	Destabilizing	0.969	D	0.603	neutral	None	None	None	None	N
S/F	0.5856	likely_pathogenic	0.5995	pathogenic	-0.884	Destabilizing	0.988	D	0.626	neutral	N	0.472916175	None	None	N
S/G	0.1589	likely_benign	0.1474	benign	-1.119	Destabilizing	0.02	N	0.197	neutral	None	None	None	None	N
S/H	0.652	likely_pathogenic	0.6617	pathogenic	-1.59	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
S/I	0.3944	ambiguous	0.4235	ambiguous	-0.074	Destabilizing	0.17	N	0.501	neutral	None	None	None	None	N
S/K	0.9394	likely_pathogenic	0.949	pathogenic	-0.595	Destabilizing	0.939	D	0.613	neutral	None	None	None	None	N
S/L	0.2394	likely_benign	0.2457	benign	-0.074	Destabilizing	0.759	D	0.577	neutral	None	None	None	None	N
S/M	0.3939	ambiguous	0.4136	ambiguous	0.073	Stabilizing	0.991	D	0.576	neutral	None	None	None	None	N
S/N	0.2858	likely_benign	0.3046	benign	-0.757	Destabilizing	0.969	D	0.585	neutral	None	None	None	None	N
S/P	0.6585	likely_pathogenic	0.6614	pathogenic	-0.283	Destabilizing	0.996	D	0.607	neutral	N	0.496895595	None	None	N
S/Q	0.8093	likely_pathogenic	0.8368	pathogenic	-0.766	Destabilizing	0.997	D	0.637	neutral	None	None	None	None	N
S/R	0.9212	likely_pathogenic	0.9276	pathogenic	-0.679	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
S/T	0.1002	likely_benign	0.1009	benign	-0.693	Destabilizing	0.061	N	0.198	neutral	N	0.457681059	None	None	N
S/V	0.3584	ambiguous	0.3765	ambiguous	-0.283	Destabilizing	0.759	D	0.578	neutral	None	None	None	None	N
S/W	0.6906	likely_pathogenic	0.6989	pathogenic	-0.908	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
S/Y	0.4817	ambiguous	0.5006	ambiguous	-0.594	Destabilizing	0.996	D	0.629	neutral	N	0.472095938	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.