TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26524	79795;79796;79797	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
N2AB	24883	74872;74873;74874	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
N2A	23956	72091;72092;72093	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
N2B	17459	52600;52601;52602	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
Novex-1	17584	52975;52976;52977	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
Novex-2	17651	53176;53177;53178	chr2:178566562;178566561;178566560	chr2:179431289;179431288;179431287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-81
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0431
• 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/A	None	None	0.834	D	0.645	0.49	0.752298016129	gnomAD-4.0.0	1.59276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
V/L	rs1705941525	None	0.263	N	0.621	0.109	0.547426921019	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs1705941525	None	0.263	N	0.621	0.109	0.547426921019	gnomAD-4.0.0	6.57635E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47098E-05	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	0.5241	ambiguous	0.5279	ambiguous	-2.153	Highly Destabilizing	0.834	D	0.645	neutral	D	0.546908536	None	None	N
V/C	0.9274	likely_pathogenic	0.9334	pathogenic	-1.628	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
V/D	0.9969	likely_pathogenic	0.9968	pathogenic	-3.345	Highly Destabilizing	0.979	D	0.888	deleterious	None	None	None	None	N
V/E	0.9901	likely_pathogenic	0.9898	pathogenic	-3.018	Highly Destabilizing	0.973	D	0.887	deleterious	D	0.55902531	None	None	N
V/F	0.7397	likely_pathogenic	0.7252	pathogenic	-1.292	Destabilizing	0.959	D	0.861	deleterious	None	None	None	None	N
V/G	0.8841	likely_pathogenic	0.8805	pathogenic	-2.761	Highly Destabilizing	0.973	D	0.883	deleterious	D	0.55902531	None	None	N
V/H	0.9965	likely_pathogenic	0.9963	pathogenic	-2.789	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/I	0.0781	likely_benign	0.0782	benign	-0.377	Destabilizing	0.016	N	0.317	neutral	N	0.488740259	None	None	N
V/K	0.9911	likely_pathogenic	0.991	pathogenic	-1.868	Destabilizing	0.979	D	0.887	deleterious	None	None	None	None	N
V/L	0.3064	likely_benign	0.3038	benign	-0.377	Destabilizing	0.263	N	0.621	neutral	N	0.503944572	None	None	N
V/M	0.3744	ambiguous	0.3652	ambiguous	-0.617	Destabilizing	0.959	D	0.791	deleterious	None	None	None	None	N
V/N	0.9884	likely_pathogenic	0.988	pathogenic	-2.624	Highly Destabilizing	0.993	D	0.889	deleterious	None	None	None	None	N
V/P	0.9838	likely_pathogenic	0.9815	pathogenic	-0.951	Destabilizing	0.993	D	0.888	deleterious	None	None	None	None	N
V/Q	0.9869	likely_pathogenic	0.9871	pathogenic	-2.237	Highly Destabilizing	0.993	D	0.899	deleterious	None	None	None	None	N
V/R	0.9847	likely_pathogenic	0.9859	pathogenic	-2.059	Highly Destabilizing	0.979	D	0.894	deleterious	None	None	None	None	N
V/S	0.9185	likely_pathogenic	0.9212	pathogenic	-3.08	Highly Destabilizing	0.979	D	0.891	deleterious	None	None	None	None	N
V/T	0.6551	likely_pathogenic	0.6536	pathogenic	-2.586	Highly Destabilizing	0.87	D	0.719	prob.delet.	None	None	None	None	N
V/W	0.9942	likely_pathogenic	0.9946	pathogenic	-1.89	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9827	likely_pathogenic	0.9824	pathogenic	-1.521	Destabilizing	0.979	D	0.859	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.