TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4911	14956;14957;14958	chr2:178735715;178735714;178735713	chr2:179600442;179600441;179600440
N2AB	4594	14005;14006;14007	chr2:178735715;178735714;178735713	chr2:179600442;179600441;179600440
N2A	3667	11224;11225;11226	chr2:178735715;178735714;178735713	chr2:179600442;179600441;179600440
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-32
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1481
• 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
V/I	rs2081325701	None	0.014	D	0.241	0.202	0.468003879618	gnomAD-4.0.0	3.4212E-06	None	None	None	None	N	None	0	0	None	0	2.52169E-05	None	0	0	3.59788E-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
V/A	0.2582	likely_benign	0.2718	benign	-2.299	Highly Destabilizing	0.014	N	0.331	neutral	D	0.52935795	None	None	N
V/C	0.8859	likely_pathogenic	0.8926	pathogenic	-1.752	Destabilizing	0.994	D	0.74	deleterious	None	None	None	None	N
V/D	0.9402	likely_pathogenic	0.9486	pathogenic	-3.215	Highly Destabilizing	0.978	D	0.836	deleterious	None	None	None	None	N
V/E	0.8957	likely_pathogenic	0.9042	pathogenic	-2.984	Highly Destabilizing	0.942	D	0.811	deleterious	D	0.760087314	None	None	N
V/F	0.4108	ambiguous	0.4356	ambiguous	-1.25	Destabilizing	0.956	D	0.783	deleterious	None	None	None	None	N
V/G	0.5178	ambiguous	0.5542	ambiguous	-2.807	Highly Destabilizing	0.89	D	0.811	deleterious	D	0.700686014	None	None	N
V/H	0.9613	likely_pathogenic	0.9664	pathogenic	-2.583	Highly Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	N
V/I	0.0966	likely_benign	0.0953	benign	-0.85	Destabilizing	0.014	N	0.241	neutral	D	0.52297544	None	None	N
V/K	0.9342	likely_pathogenic	0.9389	pathogenic	-1.903	Destabilizing	0.956	D	0.809	deleterious	None	None	None	None	N
V/L	0.3372	likely_benign	0.3633	ambiguous	-0.85	Destabilizing	0.489	N	0.604	neutral	D	0.624881722	None	None	N
V/M	0.2827	likely_benign	0.2995	benign	-0.962	Destabilizing	0.956	D	0.711	prob.delet.	None	None	None	None	N
V/N	0.8715	likely_pathogenic	0.8826	pathogenic	-2.303	Highly Destabilizing	0.978	D	0.827	deleterious	None	None	None	None	N
V/P	0.9182	likely_pathogenic	0.9285	pathogenic	-1.312	Destabilizing	0.978	D	0.805	deleterious	None	None	None	None	N
V/Q	0.9106	likely_pathogenic	0.9174	pathogenic	-2.108	Highly Destabilizing	0.978	D	0.801	deleterious	None	None	None	None	N
V/R	0.8977	likely_pathogenic	0.9011	pathogenic	-1.716	Destabilizing	0.956	D	0.819	deleterious	None	None	None	None	N
V/S	0.5919	likely_pathogenic	0.6185	pathogenic	-2.816	Highly Destabilizing	0.915	D	0.792	deleterious	None	None	None	None	N
V/T	0.3595	ambiguous	0.3743	ambiguous	-2.466	Highly Destabilizing	0.86	D	0.668	neutral	None	None	None	None	N
V/W	0.9541	likely_pathogenic	0.962	pathogenic	-1.87	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
V/Y	0.8713	likely_pathogenic	0.8798	pathogenic	-1.559	Destabilizing	0.993	D	0.761	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.