TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16212	48859;48860;48861	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
N2AB	14571	43936;43937;43938	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
N2A	13644	41155;41156;41157	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
N2B	7147	21664;21665;21666	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
Novex-1	7272	22039;22040;22041	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
Novex-2	7339	22240;22241;22242	chr2:178615311;178615310;178615309	chr2:179480038;179480037;179480036
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-5
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.2995
• 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
T/I	None	None	0.565	D	0.525	0.294	0.402043589563	gnomAD-4.0.0	1.59506E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03324E-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
T/A	0.1096	likely_benign	0.0968	benign	-0.77	Destabilizing	0.349	N	0.468	neutral	D	0.573341689	None	None	N
T/C	0.2944	likely_benign	0.2919	benign	-0.405	Destabilizing	0.996	D	0.675	prob.neutral	None	None	None	None	N
T/D	0.6595	likely_pathogenic	0.6074	pathogenic	-0.881	Destabilizing	0.923	D	0.615	neutral	None	None	None	None	N
T/E	0.4395	ambiguous	0.3761	ambiguous	-0.71	Destabilizing	0.923	D	0.605	neutral	None	None	None	None	N
T/F	0.5132	ambiguous	0.4561	ambiguous	-0.551	Destabilizing	0.923	D	0.695	prob.neutral	None	None	None	None	N
T/G	0.2601	likely_benign	0.2215	benign	-1.163	Destabilizing	0.923	D	0.615	neutral	None	None	None	None	N
T/H	0.4528	ambiguous	0.4102	ambiguous	-1.282	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
T/I	0.291	likely_benign	0.253	benign	0.248	Stabilizing	0.565	D	0.525	neutral	D	0.611481548	None	None	N
T/K	0.232	likely_benign	0.2148	benign	-0.341	Destabilizing	0.901	D	0.595	neutral	D	0.532858394	None	None	N
T/L	0.0685	likely_benign	0.0604	benign	0.248	Stabilizing	0.005	N	0.316	neutral	None	None	None	None	N
T/M	0.0712	likely_benign	0.0654	benign	0.156	Stabilizing	0.923	D	0.682	prob.neutral	None	None	None	None	N
T/N	0.1346	likely_benign	0.1174	benign	-0.915	Destabilizing	0.961	D	0.545	neutral	None	None	None	None	N
T/P	0.0916	likely_benign	0.0772	benign	-0.059	Destabilizing	0.008	N	0.397	neutral	N	0.482750597	None	None	N
T/Q	0.2363	likely_benign	0.211	benign	-0.705	Destabilizing	0.961	D	0.678	prob.neutral	None	None	None	None	N
T/R	0.2189	likely_benign	0.1944	benign	-0.499	Destabilizing	0.949	D	0.667	neutral	D	0.538543144	None	None	N
T/S	0.1928	likely_benign	0.168	benign	-1.15	Destabilizing	0.722	D	0.43	neutral	N	0.516846315	None	None	N
T/V	0.1786	likely_benign	0.1625	benign	-0.059	Destabilizing	0.633	D	0.443	neutral	None	None	None	None	N
T/W	0.8133	likely_pathogenic	0.7618	pathogenic	-0.751	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	N
T/Y	0.5032	ambiguous	0.4437	ambiguous	-0.332	Destabilizing	0.987	D	0.701	prob.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.