TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15191	45796;45797;45798	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
N2AB	13550	40873;40874;40875	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
N2A	12623	38092;38093;38094	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
N2B	6126	18601;18602;18603	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
Novex-1	6251	18976;18977;18978	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
Novex-2	6318	19177;19178;19179	chr2:178621147;178621146;178621145	chr2:179485874;179485873;179485872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-103
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0671
• 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/L	None	None	0.64	N	0.666	0.129	0.543691374674	gnomAD-4.0.0	1.59369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02828E-05

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	0.3971	ambiguous	0.4435	ambiguous	-2.161	Highly Destabilizing	0.026	N	0.414	neutral	N	0.45438068	None	None	N
V/C	0.8838	likely_pathogenic	0.8922	pathogenic	-1.471	Destabilizing	0.997	D	0.764	deleterious	None	None	None	None	N
V/D	0.9951	likely_pathogenic	0.9963	pathogenic	-3.185	Highly Destabilizing	0.984	D	0.887	deleterious	D	0.584753116	None	None	N
V/E	0.9872	likely_pathogenic	0.9892	pathogenic	-2.904	Highly Destabilizing	0.976	D	0.863	deleterious	None	None	None	None	N
V/F	0.8152	likely_pathogenic	0.8683	pathogenic	-1.233	Destabilizing	0.059	N	0.585	neutral	N	0.48428284	None	None	N
V/G	0.7482	likely_pathogenic	0.7847	pathogenic	-2.725	Highly Destabilizing	0.811	D	0.864	deleterious	D	0.584593243	None	None	N
V/H	0.9967	likely_pathogenic	0.9977	pathogenic	-2.596	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/I	0.1509	likely_benign	0.1712	benign	-0.535	Destabilizing	0.78	D	0.594	neutral	N	0.442537305	None	None	N
V/K	0.9946	likely_pathogenic	0.9955	pathogenic	-1.763	Destabilizing	0.976	D	0.865	deleterious	None	None	None	None	N
V/L	0.5488	ambiguous	0.5768	pathogenic	-0.535	Destabilizing	0.64	D	0.666	neutral	N	0.436586961	None	None	N
V/M	0.5946	likely_pathogenic	0.6548	pathogenic	-0.594	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
V/N	0.9799	likely_pathogenic	0.9847	pathogenic	-2.31	Highly Destabilizing	0.988	D	0.891	deleterious	None	None	None	None	N
V/P	0.9897	likely_pathogenic	0.9917	pathogenic	-1.058	Destabilizing	0.988	D	0.872	deleterious	None	None	None	None	N
V/Q	0.9853	likely_pathogenic	0.9884	pathogenic	-2.049	Highly Destabilizing	0.988	D	0.879	deleterious	None	None	None	None	N
V/R	0.9885	likely_pathogenic	0.9903	pathogenic	-1.755	Destabilizing	0.988	D	0.887	deleterious	None	None	None	None	N
V/S	0.8477	likely_pathogenic	0.8773	pathogenic	-2.817	Highly Destabilizing	0.851	D	0.851	deleterious	None	None	None	None	N
V/T	0.7214	likely_pathogenic	0.754	pathogenic	-2.395	Highly Destabilizing	0.919	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9992	pathogenic	-1.864	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/Y	0.9889	likely_pathogenic	0.9926	pathogenic	-1.477	Destabilizing	0.952	D	0.795	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.