TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7912	23959;23960;23961	chr2:178719758;178719757;178719756	chr2:179584485;179584484;179584483
N2AB	7595	23008;23009;23010	chr2:178719758;178719757;178719756	chr2:179584485;179584484;179584483
N2A	6668	20227;20228;20229	chr2:178719758;178719757;178719756	chr2:179584485;179584484;179584483
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-64
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1137
• 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	rs797001857	0.053	0.9	D	0.634	0.414	0.653643074943	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
V/L	rs797001857	0.053	0.9	D	0.634	0.414	0.653643074943	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs797001857	0.053	0.9	D	0.634	0.414	0.653643074943	gnomAD-4.0.0	5.12538E-06	None	None	None	None	N	None	3.38249E-05	0	None	0	0	None	0	0	4.78719E-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	0.5806	likely_pathogenic	0.6223	pathogenic	-1.917	Destabilizing	0.989	D	0.634	neutral	D	0.525064497	None	None	N
V/C	0.9498	likely_pathogenic	0.9602	pathogenic	-1.37	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/D	0.9913	likely_pathogenic	0.9948	pathogenic	-2.518	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
V/E	0.9729	likely_pathogenic	0.9826	pathogenic	-2.25	Highly Destabilizing	0.999	D	0.862	deleterious	D	0.637305825	None	None	N
V/F	0.4135	ambiguous	0.4362	ambiguous	-1.044	Destabilizing	0.296	N	0.497	neutral	None	None	None	None	N
V/G	0.8215	likely_pathogenic	0.84	pathogenic	-2.505	Highly Destabilizing	0.999	D	0.851	deleterious	D	0.586229601	None	None	N
V/H	0.9891	likely_pathogenic	0.9927	pathogenic	-2.319	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.1014	likely_benign	0.126	benign	-0.257	Destabilizing	0.96	D	0.582	neutral	None	None	None	None	N
V/K	0.9835	likely_pathogenic	0.9898	pathogenic	-1.625	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/L	0.4674	ambiguous	0.5908	pathogenic	-0.257	Destabilizing	0.9	D	0.634	neutral	D	0.558178757	None	None	N
V/M	0.4417	ambiguous	0.5309	ambiguous	-0.315	Destabilizing	0.999	D	0.739	prob.delet.	D	0.611364105	None	None	N
V/N	0.9791	likely_pathogenic	0.9865	pathogenic	-2.086	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/P	0.981	likely_pathogenic	0.9878	pathogenic	-0.784	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9728	likely_pathogenic	0.9809	pathogenic	-1.824	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/R	0.97	likely_pathogenic	0.9786	pathogenic	-1.611	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
V/S	0.8775	likely_pathogenic	0.898	pathogenic	-2.71	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
V/T	0.7249	likely_pathogenic	0.7753	pathogenic	-2.282	Highly Destabilizing	0.997	D	0.706	prob.neutral	None	None	None	None	N
V/W	0.9836	likely_pathogenic	0.9877	pathogenic	-1.621	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/Y	0.9355	likely_pathogenic	0.9475	pathogenic	-1.184	Destabilizing	0.99	D	0.822	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.