TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4665	14218;14219;14220	chr2:178739240;178739239;178739238	chr2:179603967;179603966;179603965
N2AB	4348	13267;13268;13269	chr2:178739240;178739239;178739238	chr2:179603967;179603966;179603965
N2A	None	None	chr2:None	chr2:None
N2B	4302	13129;13130;13131	chr2:178739240;178739239;178739238	chr2:179603967;179603966;179603965
Novex-1	4427	13504;13505;13506	chr2:178739240;178739239;178739238	chr2:179603967;179603966;179603965
Novex-2	4494	13705;13706;13707	chr2:178739240;178739239;178739238	chr2:179603967;179603966;179603965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-29
• Domain position: 60
• Structural Position: 143
• Q(SASA): 0.6185
• 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
K/R	None	None	None	N	0.243	0.091	0.0401082797425	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.1533	likely_benign	0.1782	benign	-0.1	Destabilizing	None	N	0.21	neutral	None	None	None	None	N
K/C	0.4724	ambiguous	0.5046	ambiguous	-0.079	Destabilizing	0.676	D	0.297	neutral	None	None	None	None	N
K/D	0.2419	likely_benign	0.2621	benign	0.07	Stabilizing	0.038	N	0.345	neutral	None	None	None	None	N
K/E	0.0927	likely_benign	0.1008	benign	0.107	Stabilizing	None	N	0.178	neutral	N	0.445002694	None	None	N
K/F	0.5156	ambiguous	0.5669	pathogenic	-0.088	Destabilizing	0.356	N	0.323	neutral	None	None	None	None	N
K/G	0.2316	likely_benign	0.2626	benign	-0.366	Destabilizing	None	N	0.211	neutral	None	None	None	None	N
K/H	0.1851	likely_benign	0.1964	benign	-0.65	Destabilizing	0.214	N	0.309	neutral	None	None	None	None	N
K/I	0.2255	likely_benign	0.2601	benign	0.542	Stabilizing	0.093	N	0.35	neutral	D	0.571782789	None	None	N
K/L	0.2163	likely_benign	0.2456	benign	0.542	Stabilizing	0.038	N	0.396	neutral	None	None	None	None	N
K/M	0.1212	likely_benign	0.1386	benign	0.359	Stabilizing	0.356	N	0.315	neutral	None	None	None	None	N
K/N	0.149	likely_benign	0.1657	benign	0.212	Stabilizing	None	N	0.233	neutral	N	0.436681842	None	None	N
K/P	0.6216	likely_pathogenic	0.7072	pathogenic	0.358	Stabilizing	0.072	N	0.371	neutral	None	None	None	None	N
K/Q	0.1052	likely_benign	0.1084	benign	0.06	Stabilizing	0.001	N	0.148	neutral	N	0.452024597	None	None	N
K/R	0.0816	likely_benign	0.0879	benign	-0.109	Destabilizing	None	N	0.243	neutral	N	0.453338578	None	None	N
K/S	0.1736	likely_benign	0.2036	benign	-0.316	Destabilizing	0.001	N	0.203	neutral	None	None	None	None	N
K/T	0.0743	likely_benign	0.0881	benign	-0.112	Destabilizing	None	N	0.211	neutral	N	0.454070441	None	None	N
K/V	0.2006	likely_benign	0.2276	benign	0.358	Stabilizing	0.038	N	0.367	neutral	None	None	None	None	N
K/W	0.5932	likely_pathogenic	0.6326	pathogenic	-0.054	Destabilizing	0.864	D	0.342	neutral	None	None	None	None	N
K/Y	0.3734	ambiguous	0.4057	ambiguous	0.26	Stabilizing	0.356	N	0.316	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.