TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34451	103576;103577;103578	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
N2AB	32810	98653;98654;98655	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
N2A	31883	95872;95873;95874	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
N2B	25386	76381;76382;76383	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
Novex-1	25511	76756;76757;76758	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
Novex-2	25578	76957;76958;76959	chr2:178533264;178533263;178533262	chr2:179397991;179397990;179397989
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-162
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.0953
• 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	rs1559023612	None	0.928	D	0.651	0.687	0.562392168299	gnomAD-4.0.0	1.59093E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85762E-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
L/A	0.9925	likely_pathogenic	0.9912	pathogenic	-3.054	Highly Destabilizing	0.895	D	0.741	deleterious	None	None	None	None	N
L/C	0.9837	likely_pathogenic	0.9816	pathogenic	-2.502	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.81	Highly Destabilizing	0.983	D	0.905	deleterious	None	None	None	None	N
L/E	0.9992	likely_pathogenic	0.9992	pathogenic	-3.549	Highly Destabilizing	0.983	D	0.913	deleterious	None	None	None	None	N
L/F	0.9335	likely_pathogenic	0.9269	pathogenic	-1.845	Destabilizing	0.997	D	0.837	deleterious	None	None	None	None	N
L/G	0.9982	likely_pathogenic	0.9982	pathogenic	-3.62	Highly Destabilizing	0.983	D	0.908	deleterious	None	None	None	None	N
L/H	0.9982	likely_pathogenic	0.9979	pathogenic	-3.154	Highly Destabilizing	0.999	D	0.91	deleterious	None	None	None	None	N
L/I	0.4653	ambiguous	0.4276	ambiguous	-1.369	Destabilizing	0.963	D	0.652	neutral	D	0.565118671	None	None	N
L/K	0.9976	likely_pathogenic	0.9976	pathogenic	-2.499	Highly Destabilizing	0.983	D	0.895	deleterious	None	None	None	None	N
L/M	0.7557	likely_pathogenic	0.73	pathogenic	-1.408	Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
L/N	0.9994	likely_pathogenic	0.9993	pathogenic	-3.037	Highly Destabilizing	0.992	D	0.913	deleterious	None	None	None	None	N
L/P	0.9996	likely_pathogenic	0.9996	pathogenic	-1.919	Destabilizing	0.085	N	0.667	neutral	D	0.644931514	None	None	N
L/Q	0.9971	likely_pathogenic	0.9969	pathogenic	-2.819	Highly Destabilizing	0.989	D	0.908	deleterious	D	0.644931514	None	None	N
L/R	0.9944	likely_pathogenic	0.9946	pathogenic	-2.218	Highly Destabilizing	0.989	D	0.899	deleterious	D	0.644931514	None	None	N
L/S	0.9993	likely_pathogenic	0.9991	pathogenic	-3.655	Highly Destabilizing	0.983	D	0.884	deleterious	None	None	None	None	N
L/T	0.9948	likely_pathogenic	0.9939	pathogenic	-3.25	Highly Destabilizing	0.983	D	0.836	deleterious	None	None	None	None	N
L/V	0.6106	likely_pathogenic	0.5696	pathogenic	-1.919	Destabilizing	0.928	D	0.651	neutral	D	0.541398592	None	None	N
L/W	0.9957	likely_pathogenic	0.9958	pathogenic	-2.357	Highly Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
L/Y	0.9956	likely_pathogenic	0.9955	pathogenic	-2.165	Highly Destabilizing	0.997	D	0.864	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.