TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7233	21922;21923;21924	chr2:178723310;178723309;178723308	chr2:179588037;179588036;179588035
N2AB	6916	20971;20972;20973	chr2:178723310;178723309;178723308	chr2:179588037;179588036;179588035
N2A	5989	18190;18191;18192	chr2:178723310;178723309;178723308	chr2:179588037;179588036;179588035
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-57
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4075
• Predicted PPI site: I

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
L/F	rs370679926	None	0.055	N	0.218	0.136	0.374434639691	gnomAD-4.0.0	1.37052E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80061E-06	0	0
L/M	None	None	0.001	N	0.126	0.103	0.400899426204	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
L/A	0.1174	likely_benign	0.137	benign	-0.614	Destabilizing	0.007	N	0.135	neutral	None	None	None	None	I
L/C	0.3421	ambiguous	0.3822	ambiguous	-0.608	Destabilizing	0.356	N	0.297	neutral	None	None	None	None	I
L/D	0.39	ambiguous	0.42	ambiguous	-0.126	Destabilizing	0.072	N	0.327	neutral	None	None	None	None	I
L/E	0.163	likely_benign	0.1712	benign	-0.211	Destabilizing	0.031	N	0.237	neutral	None	None	None	None	I
L/F	0.0904	likely_benign	0.109	benign	-0.575	Destabilizing	0.055	N	0.218	neutral	N	0.459379098	None	None	I
L/G	0.2484	likely_benign	0.2682	benign	-0.786	Destabilizing	0.031	N	0.217	neutral	None	None	None	None	I
L/H	0.142	likely_benign	0.1626	benign	-0.031	Destabilizing	0.628	D	0.288	neutral	None	None	None	None	I
L/I	0.0535	likely_benign	0.0585	benign	-0.279	Destabilizing	0.002	N	0.091	neutral	None	None	None	None	I
L/K	0.1466	likely_benign	0.1493	benign	-0.353	Destabilizing	None	N	0.16	neutral	None	None	None	None	I
L/M	0.0808	likely_benign	0.0957	benign	-0.373	Destabilizing	0.001	N	0.126	neutral	N	0.477317252	None	None	I
L/N	0.1866	likely_benign	0.2022	benign	-0.144	Destabilizing	0.072	N	0.327	neutral	None	None	None	None	I
L/P	0.5284	ambiguous	0.4843	ambiguous	-0.357	Destabilizing	0.136	N	0.381	neutral	None	None	None	None	I
L/Q	0.0856	likely_benign	0.0937	benign	-0.358	Destabilizing	0.072	N	0.363	neutral	None	None	None	None	I
L/R	0.1106	likely_benign	0.1132	benign	0.202	Stabilizing	0.038	N	0.293	neutral	None	None	None	None	I
L/S	0.1113	likely_benign	0.1329	benign	-0.615	Destabilizing	0.001	N	0.149	neutral	N	0.46898577	None	None	I
L/T	0.0919	likely_benign	0.1021	benign	-0.591	Destabilizing	0.016	N	0.228	neutral	None	None	None	None	I
L/V	0.0473	likely_benign	0.053	benign	-0.357	Destabilizing	None	N	0.089	neutral	N	0.37064836	None	None	I
L/W	0.1858	likely_benign	0.217	benign	-0.592	Destabilizing	0.828	D	0.266	neutral	N	0.459886077	None	None	I
L/Y	0.2305	likely_benign	0.2732	benign	-0.347	Destabilizing	0.356	N	0.385	neutral	None	None	None	None	I

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.