TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9985	30178;30179;30180	chr2:178704519;178704518;178704517	chr2:179569246;179569245;179569244
N2AB	9668	29227;29228;29229	chr2:178704519;178704518;178704517	chr2:179569246;179569245;179569244
N2A	8741	26446;26447;26448	chr2:178704519;178704518;178704517	chr2:179569246;179569245;179569244
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-84
• Domain position: 86
• Structural Position: 175
• Q(SASA): 0.2401
• 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	rs1339300021	None	0.379	None	0.514	0.328	0.326074293725	gnomAD-4.0.0	4.82177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.75377E-04	3.61473E-06	0	3.33901E-05
T/S	None	None	0.016	None	0.345	0.067	0.104622674875	gnomAD-4.0.0	6.88825E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03684E-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
T/A	0.2503	likely_benign	0.2343	benign	-0.872	Destabilizing	0.004	N	0.32	neutral	None	None	None	None	N
T/C	0.858	likely_pathogenic	0.8575	pathogenic	-0.655	Destabilizing	0.977	D	0.51	neutral	None	None	None	None	N
T/D	0.7816	likely_pathogenic	0.7398	pathogenic	-0.371	Destabilizing	0.447	N	0.508	neutral	None	None	None	None	N
T/E	0.6252	likely_pathogenic	0.591	pathogenic	-0.338	Destabilizing	0.021	N	0.317	neutral	None	None	None	None	N
T/F	0.5829	likely_pathogenic	0.5418	ambiguous	-0.776	Destabilizing	0.92	D	0.579	neutral	None	None	None	None	N
T/G	0.7722	likely_pathogenic	0.7649	pathogenic	-1.163	Destabilizing	0.447	N	0.503	neutral	None	None	None	None	N
T/H	0.5442	ambiguous	0.4986	ambiguous	-1.38	Destabilizing	0.992	D	0.583	neutral	None	None	None	None	N
T/I	0.3541	ambiguous	0.327	benign	-0.175	Destabilizing	0.379	N	0.514	neutral	None	None	None	None	N
T/K	0.5253	ambiguous	0.489	ambiguous	-0.782	Destabilizing	0.617	D	0.509	neutral	None	None	None	None	N
T/L	0.2424	likely_benign	0.233	benign	-0.175	Destabilizing	0.447	N	0.427	neutral	None	None	None	None	N
T/M	0.1612	likely_benign	0.1529	benign	0.009	Stabilizing	0.92	D	0.505	neutral	None	None	None	None	N
T/N	0.3336	likely_benign	0.2897	benign	-0.815	Destabilizing	0.81	D	0.459	neutral	None	None	None	None	N
T/P	0.8921	likely_pathogenic	0.8937	pathogenic	-0.374	Destabilizing	0.896	D	0.52	neutral	None	None	None	None	N
T/Q	0.4896	ambiguous	0.4528	ambiguous	-0.941	Destabilizing	0.85	D	0.525	neutral	None	None	None	None	N
T/R	0.4589	ambiguous	0.4184	ambiguous	-0.588	Destabilizing	0.85	D	0.527	neutral	None	None	None	None	N
T/S	0.3232	likely_benign	0.2876	benign	-1.115	Destabilizing	0.016	N	0.345	neutral	None	None	None	None	N
T/V	0.2756	likely_benign	0.2698	benign	-0.374	Destabilizing	0.021	N	0.317	neutral	None	None	None	None	N
T/W	0.8831	likely_pathogenic	0.8694	pathogenic	-0.706	Destabilizing	0.992	D	0.629	neutral	None	None	None	None	N
T/Y	0.6553	likely_pathogenic	0.6344	pathogenic	-0.472	Destabilizing	0.972	D	0.584	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.