TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24132	72619;72620;72621	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
N2AB	22491	67696;67697;67698	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
N2A	21564	64915;64916;64917	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
N2B	15067	45424;45425;45426	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
Novex-1	15192	45799;45800;45801	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
Novex-2	15259	46000;46001;46002	chr2:178573738;178573737;178573736	chr2:179438465;179438464;179438463
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: Fn3-63
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.3093
• 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/I	rs727504188	None	0.767	N	0.301	0.192	0.40722173914	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/I	rs727504188	None	0.767	N	0.301	0.192	0.40722173914	gnomAD-4.0.0	5.11185E-06	None	None	None	None	N	None	1.37118E-05	0	None	0	0	None	0	0	6.04188E-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
V/A	0.3763	ambiguous	0.4701	ambiguous	-1.392	Destabilizing	0.998	D	0.564	neutral	N	0.518846948	None	None	N
V/C	0.7912	likely_pathogenic	0.8327	pathogenic	-1.193	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/D	0.9137	likely_pathogenic	0.9415	pathogenic	-0.542	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/E	0.8553	likely_pathogenic	0.8906	pathogenic	-0.462	Destabilizing	1.0	D	0.887	deleterious	D	0.549833554	None	None	N
V/F	0.2677	likely_benign	0.3569	ambiguous	-0.864	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/G	0.5802	likely_pathogenic	0.6653	pathogenic	-1.791	Destabilizing	1.0	D	0.881	deleterious	N	0.514586096	None	None	N
V/H	0.9254	likely_pathogenic	0.9462	pathogenic	-1.271	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.073	likely_benign	0.0766	benign	-0.374	Destabilizing	0.767	D	0.301	neutral	N	0.479637986	None	None	N
V/K	0.8638	likely_pathogenic	0.8865	pathogenic	-1.01	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/L	0.271	likely_benign	0.3588	ambiguous	-0.374	Destabilizing	0.981	D	0.471	neutral	N	0.478133642	None	None	N
V/M	0.2147	likely_benign	0.2901	benign	-0.494	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/N	0.7956	likely_pathogenic	0.853	pathogenic	-0.946	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/P	0.7425	likely_pathogenic	0.8303	pathogenic	-0.678	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/Q	0.8395	likely_pathogenic	0.8743	pathogenic	-0.927	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/R	0.829	likely_pathogenic	0.857	pathogenic	-0.754	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/S	0.6162	likely_pathogenic	0.7012	pathogenic	-1.667	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/T	0.5077	ambiguous	0.5905	pathogenic	-1.438	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
V/W	0.938	likely_pathogenic	0.9612	pathogenic	-1.057	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Y	0.7945	likely_pathogenic	0.8483	pathogenic	-0.731	Destabilizing	1.0	D	0.881	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.