TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25772	77539;77540;77541	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
N2AB	24131	72616;72617;72618	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
N2A	23204	69835;69836;69837	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
N2B	16707	50344;50345;50346	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
Novex-1	16832	50719;50720;50721	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
Novex-2	16899	50920;50921;50922	chr2:178568818;178568817;178568816	chr2:179433545;179433544;179433543
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-75
• Domain position: 75
• Structural Position: 109
• Q(SASA): 0.0789
• 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	None	None	None	N	0.181	0.045	0.240491677333	gnomAD-4.0.0	6.84437E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99604E-07	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	0.1328	likely_benign	0.1287	benign	-2.449	Highly Destabilizing	None	N	0.25	neutral	N	0.411100621	None	None	N
V/C	0.561	ambiguous	0.5493	ambiguous	-1.982	Destabilizing	0.628	D	0.666	neutral	None	None	None	None	N
V/D	0.6437	likely_pathogenic	0.6102	pathogenic	-3.267	Highly Destabilizing	0.171	N	0.691	prob.neutral	N	0.471622274	None	None	N
V/E	0.4378	ambiguous	0.4177	ambiguous	-3.079	Highly Destabilizing	0.072	N	0.657	neutral	None	None	None	None	N
V/F	0.1436	likely_benign	0.1323	benign	-1.386	Destabilizing	None	N	0.631	neutral	N	0.419914892	None	None	N
V/G	0.3073	likely_benign	0.3047	benign	-2.909	Highly Destabilizing	0.029	N	0.67	neutral	N	0.504936288	None	None	N
V/H	0.5823	likely_pathogenic	0.5479	ambiguous	-2.499	Highly Destabilizing	0.864	D	0.66	neutral	None	None	None	None	N
V/I	0.0786	likely_benign	0.0714	benign	-1.158	Destabilizing	None	N	0.181	neutral	N	0.380876501	None	None	N
V/K	0.5232	ambiguous	0.5036	ambiguous	-2.058	Highly Destabilizing	0.072	N	0.654	neutral	None	None	None	None	N
V/L	0.1667	likely_benign	0.151	benign	-1.158	Destabilizing	0.002	N	0.412	neutral	N	0.438615296	None	None	N
V/M	0.0949	likely_benign	0.0895	benign	-1.303	Destabilizing	0.003	N	0.41	neutral	None	None	None	None	N
V/N	0.4187	ambiguous	0.374	ambiguous	-2.342	Highly Destabilizing	0.214	N	0.689	prob.neutral	None	None	None	None	N
V/P	0.9781	likely_pathogenic	0.9683	pathogenic	-1.567	Destabilizing	0.356	N	0.679	prob.neutral	None	None	None	None	N
V/Q	0.3737	ambiguous	0.3593	ambiguous	-2.239	Highly Destabilizing	0.214	N	0.665	neutral	None	None	None	None	N
V/R	0.43	ambiguous	0.4182	ambiguous	-1.74	Destabilizing	0.214	N	0.691	prob.neutral	None	None	None	None	N
V/S	0.1651	likely_benign	0.1601	benign	-2.855	Highly Destabilizing	None	N	0.498	neutral	None	None	None	None	N
V/T	0.1252	likely_benign	0.1254	benign	-2.556	Highly Destabilizing	0.016	N	0.539	neutral	None	None	None	None	N
V/W	0.7554	likely_pathogenic	0.753	pathogenic	-1.871	Destabilizing	0.864	D	0.67	neutral	None	None	None	None	N
V/Y	0.5174	ambiguous	0.4806	ambiguous	-1.616	Destabilizing	0.12	N	0.715	prob.delet.	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.