TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7381	22366;22367;22368	chr2:178722758;178722757;178722756	chr2:179587485;179587484;179587483
N2AB	7064	21415;21416;21417	chr2:178722758;178722757;178722756	chr2:179587485;179587484;179587483
N2A	6137	18634;18635;18636	chr2:178722758;178722757;178722756	chr2:179587485;179587484;179587483
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-58
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2718
• 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
V/L	rs762179106	-0.122	0.057	N	0.333	0.145	0.488196290542	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
V/L	rs762179106	-0.122	0.057	N	0.333	0.145	0.488196290542	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs762179106	-0.122	0.057	N	0.333	0.145	0.488196290542	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	2.41383E-05	0	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
V/A	0.2022	likely_benign	0.4134	ambiguous	-1.706	Destabilizing	0.006	N	0.213	neutral	D	0.534000907	None	None	N
V/C	0.8002	likely_pathogenic	0.8993	pathogenic	-1.35	Destabilizing	0.992	D	0.495	neutral	None	None	None	None	N
V/D	0.4552	ambiguous	0.7736	pathogenic	-1.785	Destabilizing	0.688	D	0.463	neutral	D	0.522034474	None	None	N
V/E	0.3377	likely_benign	0.6086	pathogenic	-1.606	Destabilizing	0.013	N	0.349	neutral	None	None	None	None	N
V/F	0.174	likely_benign	0.3235	benign	-1.009	Destabilizing	0.966	D	0.555	neutral	N	0.502928638	None	None	N
V/G	0.2838	likely_benign	0.5536	ambiguous	-2.2	Highly Destabilizing	0.749	D	0.446	neutral	N	0.490594308	None	None	N
V/H	0.4966	ambiguous	0.7526	pathogenic	-1.913	Destabilizing	0.994	D	0.537	neutral	None	None	None	None	N
V/I	0.081	likely_benign	0.0945	benign	-0.359	Destabilizing	0.002	N	0.196	neutral	N	0.463004813	None	None	N
V/K	0.4032	ambiguous	0.676	pathogenic	-1.178	Destabilizing	0.027	N	0.35	neutral	None	None	None	None	N
V/L	0.1848	likely_benign	0.3349	benign	-0.359	Destabilizing	0.057	N	0.333	neutral	N	0.475376678	None	None	N
V/M	0.1734	likely_benign	0.3038	benign	-0.532	Destabilizing	0.964	D	0.456	neutral	None	None	None	None	N
V/N	0.3044	likely_benign	0.5829	pathogenic	-1.367	Destabilizing	0.426	N	0.541	neutral	None	None	None	None	N
V/P	0.9298	likely_pathogenic	0.9799	pathogenic	-0.778	Destabilizing	0.601	D	0.521	neutral	None	None	None	None	N
V/Q	0.3217	likely_benign	0.5482	ambiguous	-1.258	Destabilizing	0.78	D	0.518	neutral	None	None	None	None	N
V/R	0.3241	likely_benign	0.5647	pathogenic	-1.071	Destabilizing	0.842	D	0.517	neutral	None	None	None	None	N
V/S	0.2055	likely_benign	0.4311	ambiguous	-2.047	Highly Destabilizing	0.543	D	0.408	neutral	None	None	None	None	N
V/T	0.202	likely_benign	0.3956	ambiguous	-1.725	Destabilizing	0.013	N	0.179	neutral	None	None	None	None	N
V/W	0.8248	likely_pathogenic	0.9408	pathogenic	-1.426	Destabilizing	1.0	D	0.559	neutral	None	None	None	None	N
V/Y	0.5172	ambiguous	0.7135	pathogenic	-1.025	Destabilizing	0.996	D	0.545	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.