TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9028	27307;27308;27309	chr2:178712943;178712942;178712941	chr2:179577670;179577669;179577668
N2AB	8711	26356;26357;26358	chr2:178712943;178712942;178712941	chr2:179577670;179577669;179577668
N2A	7784	23575;23576;23577	chr2:178712943;178712942;178712941	chr2:179577670;179577669;179577668
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-76
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.1231
• 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
M/V	rs2076878438	None	0.028	N	0.305	0.102	0.115124310173	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
M/A	0.1549	likely_benign	0.1764	benign	-2.378	Highly Destabilizing	0.001	N	0.121	neutral	None	None	None	None	N
M/C	0.6179	likely_pathogenic	0.6672	pathogenic	-1.544	Destabilizing	0.901	D	0.38	neutral	None	None	None	None	N
M/D	0.5687	likely_pathogenic	0.6682	pathogenic	-1.103	Destabilizing	0.296	N	0.432	neutral	None	None	None	None	N
M/E	0.2027	likely_benign	0.2504	benign	-0.994	Destabilizing	0.08	N	0.328	neutral	None	None	None	None	N
M/F	0.2585	likely_benign	0.2957	benign	-1.027	Destabilizing	0.001	N	0.141	neutral	None	None	None	None	N
M/G	0.3728	ambiguous	0.4271	ambiguous	-2.764	Highly Destabilizing	0.08	N	0.353	neutral	None	None	None	None	N
M/H	0.3261	likely_benign	0.3785	ambiguous	-1.777	Destabilizing	0.749	D	0.425	neutral	None	None	None	None	N
M/I	0.128	likely_benign	0.1538	benign	-1.318	Destabilizing	0.061	N	0.342	neutral	N	0.401012205	None	None	N
M/K	0.0849	likely_benign	0.093	benign	-1.182	Destabilizing	0.002	N	0.129	neutral	N	0.435415567	None	None	N
M/L	0.0868	likely_benign	0.0894	benign	-1.318	Destabilizing	None	N	0.05	neutral	N	0.38648547	None	None	N
M/N	0.3342	likely_benign	0.4189	ambiguous	-1.158	Destabilizing	0.46	N	0.445	neutral	None	None	None	None	N
M/P	0.8068	likely_pathogenic	0.8755	pathogenic	-1.65	Destabilizing	0.46	N	0.451	neutral	None	None	None	None	N
M/Q	0.1242	likely_benign	0.1423	benign	-1.111	Destabilizing	0.007	N	0.075	neutral	None	None	None	None	N
M/R	0.0893	likely_benign	0.1029	benign	-0.773	Destabilizing	0.061	N	0.376	neutral	N	0.442592255	None	None	N
M/S	0.221	likely_benign	0.2583	benign	-1.815	Destabilizing	0.08	N	0.342	neutral	None	None	None	None	N
M/T	0.0903	likely_benign	0.1044	benign	-1.589	Destabilizing	0.116	N	0.344	neutral	N	0.440648028	None	None	N
M/V	0.0539	likely_benign	0.0568	benign	-1.65	Destabilizing	0.028	N	0.305	neutral	N	0.352658111	None	None	N
M/W	0.5312	ambiguous	0.5996	pathogenic	-1.012	Destabilizing	0.901	D	0.368	neutral	None	None	None	None	N
M/Y	0.4886	ambiguous	0.5622	ambiguous	-1.116	Destabilizing	0.174	N	0.423	neutral	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.