TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5037	15334;15335;15336	chr2:178734815;178734814;178734813	chr2:179599542;179599541;179599540
N2AB	4720	14383;14384;14385	chr2:178734815;178734814;178734813	chr2:179599542;179599541;179599540
N2A	3793	11602;11603;11604	chr2:178734815;178734814;178734813	chr2:179599542;179599541;179599540
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-33
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.0811
• 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
A/V	rs2081160946	None	1.0	N	0.634	0.364	0.363944505237	gnomAD-4.0.0	1.32035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44375E-05	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
A/C	0.8672	likely_pathogenic	0.8047	pathogenic	-0.858	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/D	0.9847	likely_pathogenic	0.985	pathogenic	-2.499	Highly Destabilizing	1.0	D	0.841	deleterious	N	0.50280466	None	None	N
A/E	0.9775	likely_pathogenic	0.9737	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
A/F	0.8728	likely_pathogenic	0.8807	pathogenic	-0.687	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/G	0.3024	likely_benign	0.3062	benign	-1.663	Destabilizing	1.0	D	0.598	neutral	N	0.452563784	None	None	N
A/H	0.9864	likely_pathogenic	0.9838	pathogenic	-2.205	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/I	0.7561	likely_pathogenic	0.7357	pathogenic	0.182	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/K	0.9945	likely_pathogenic	0.993	pathogenic	-1.127	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/L	0.6852	likely_pathogenic	0.6413	pathogenic	0.182	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/M	0.6956	likely_pathogenic	0.687	pathogenic	0.031	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/N	0.9577	likely_pathogenic	0.9514	pathogenic	-1.518	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/P	0.9849	likely_pathogenic	0.9741	pathogenic	-0.233	Destabilizing	1.0	D	0.824	deleterious	N	0.466561099	None	None	N
A/Q	0.9739	likely_pathogenic	0.9678	pathogenic	-1.242	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/R	0.986	likely_pathogenic	0.9827	pathogenic	-1.342	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/S	0.389	ambiguous	0.3565	ambiguous	-1.872	Destabilizing	1.0	D	0.603	neutral	N	0.446961528	None	None	N
A/T	0.5215	ambiguous	0.4501	ambiguous	-1.514	Destabilizing	1.0	D	0.72	prob.delet.	N	0.438753715	None	None	N
A/V	0.4292	ambiguous	0.4016	ambiguous	-0.233	Destabilizing	1.0	D	0.634	neutral	N	0.432959001	None	None	N
A/W	0.9905	likely_pathogenic	0.9898	pathogenic	-1.58	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/Y	0.9454	likely_pathogenic	0.9468	pathogenic	-1.025	Destabilizing	1.0	D	0.851	deleterious	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.