TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8095	24508;24509;24510	chr2:178718917;178718916;178718915	chr2:179583644;179583643;179583642
N2AB	7778	23557;23558;23559	chr2:178718917;178718916;178718915	chr2:179583644;179583643;179583642
N2A	6851	20776;20777;20778	chr2:178718917;178718916;178718915	chr2:179583644;179583643;179583642
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: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-66
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.0743
• 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
L/V	rs2077909849	None	None	N	0.185	0.066	0.117506650769	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/V	rs2077909849	None	None	N	0.185	0.066	0.117506650769	gnomAD-4.0.0	6.5754E-06	None	None	None	None	N	None	0	6.55136E-05	None	0	0	None	0	0	0	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	0.2355	likely_benign	0.2323	benign	-2.024	Highly Destabilizing	0.116	N	0.562	neutral	None	None	None	None	N
L/C	0.379	ambiguous	0.3959	ambiguous	-1.636	Destabilizing	0.944	D	0.697	prob.neutral	None	None	None	None	N
L/D	0.8072	likely_pathogenic	0.8221	pathogenic	-1.174	Destabilizing	0.69	D	0.753	deleterious	None	None	None	None	N
L/E	0.4621	ambiguous	0.4938	ambiguous	-1.012	Destabilizing	0.241	N	0.691	prob.neutral	None	None	None	None	N
L/F	0.1411	likely_benign	0.1444	benign	-1.148	Destabilizing	0.627	D	0.723	prob.delet.	N	0.491227912	None	None	N
L/G	0.6138	likely_pathogenic	0.5944	pathogenic	-2.481	Highly Destabilizing	0.563	D	0.71	prob.delet.	None	None	None	None	N
L/H	0.2519	likely_benign	0.2806	benign	-1.509	Destabilizing	0.928	D	0.72	prob.delet.	N	0.507178799	None	None	N
L/I	0.0599	likely_benign	0.0625	benign	-0.758	Destabilizing	0.001	N	0.247	neutral	N	0.415959362	None	None	N
L/K	0.3142	likely_benign	0.3408	ambiguous	-1.436	Destabilizing	0.241	N	0.677	prob.neutral	None	None	None	None	N
L/M	0.1025	likely_benign	0.1085	benign	-0.882	Destabilizing	0.69	D	0.676	prob.neutral	None	None	None	None	N
L/N	0.5157	ambiguous	0.5282	ambiguous	-1.631	Destabilizing	0.818	D	0.755	deleterious	None	None	None	None	N
L/P	0.8271	likely_pathogenic	0.835	pathogenic	-1.155	Destabilizing	0.912	D	0.753	deleterious	N	0.514990206	None	None	N
L/Q	0.2026	likely_benign	0.217	benign	-1.518	Destabilizing	0.054	N	0.537	neutral	None	None	None	None	N
L/R	0.211	likely_benign	0.2321	benign	-1.138	Destabilizing	0.627	D	0.734	prob.delet.	N	0.460152793	None	None	N
L/S	0.3435	ambiguous	0.3252	benign	-2.427	Highly Destabilizing	0.388	N	0.666	neutral	None	None	None	None	N
L/T	0.2076	likely_benign	0.2181	benign	-2.102	Highly Destabilizing	0.388	N	0.639	neutral	None	None	None	None	N
L/V	0.0528	likely_benign	0.055	benign	-1.155	Destabilizing	None	N	0.185	neutral	N	0.328278875	None	None	N
L/W	0.357	ambiguous	0.3923	ambiguous	-1.23	Destabilizing	0.981	D	0.688	prob.neutral	None	None	None	None	N
L/Y	0.3657	ambiguous	0.3981	ambiguous	-1.013	Destabilizing	0.818	D	0.745	deleterious	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.