TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31705	95338;95339;95340	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
N2AB	30064	90415;90416;90417	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
N2A	29137	87634;87635;87636	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
N2B	22640	68143;68144;68145	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
Novex-1	22765	68518;68519;68520	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
Novex-2	22832	68719;68720;68721	chr2:178546218;178546217;178546216	chr2:179410945;179410944;179410943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-152
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.4346
• Predicted PPI site: I

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/A	None	None	0.999	D	0.753	0.801	0.837563285501	gnomAD-4.0.0	1.60676E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89183E-06	0	0
V/L	None	None	0.997	D	0.758	0.772	0.792235188203	gnomAD-4.0.0	1.60598E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88989E-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	0.9647	likely_pathogenic	0.9786	pathogenic	-1.787	Destabilizing	0.999	D	0.753	deleterious	D	0.631055226	None	None	I
V/C	0.989	likely_pathogenic	0.9933	pathogenic	-1.447	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
V/D	0.9985	likely_pathogenic	0.9989	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	I
V/E	0.9963	likely_pathogenic	0.9972	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.615641278	None	None	I
V/F	0.9773	likely_pathogenic	0.9864	pathogenic	-1.414	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
V/G	0.9722	likely_pathogenic	0.979	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.795	deleterious	D	0.631660639	None	None	I
V/H	0.9991	likely_pathogenic	0.9994	pathogenic	-1.627	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
V/I	0.1422	likely_benign	0.189	benign	-0.948	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	I
V/K	0.9975	likely_pathogenic	0.998	pathogenic	-1.457	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
V/L	0.9366	likely_pathogenic	0.9659	pathogenic	-0.948	Destabilizing	0.997	D	0.758	deleterious	D	0.603499072	None	None	I
V/M	0.9472	likely_pathogenic	0.973	pathogenic	-0.828	Destabilizing	1.0	D	0.873	deleterious	D	0.631257031	None	None	I
V/N	0.9926	likely_pathogenic	0.9944	pathogenic	-1.387	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
V/P	0.9918	likely_pathogenic	0.9935	pathogenic	-1.197	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
V/Q	0.9971	likely_pathogenic	0.998	pathogenic	-1.583	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
V/R	0.9952	likely_pathogenic	0.9961	pathogenic	-0.939	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
V/S	0.9855	likely_pathogenic	0.9903	pathogenic	-1.88	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
V/T	0.9677	likely_pathogenic	0.9746	pathogenic	-1.754	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	I
V/W	0.9997	likely_pathogenic	0.9998	pathogenic	-1.632	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
V/Y	0.9966	likely_pathogenic	0.9977	pathogenic	-1.344	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I

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.