TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33568	100927;100928;100929	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
N2AB	31927	96004;96005;96006	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
N2A	31000	93223;93224;93225	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
N2B	24503	73732;73733;73734	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
Novex-1	24628	74107;74108;74109	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
Novex-2	24695	74308;74309;74310	chr2:178536045;178536044;178536043	chr2:179400772;179400771;179400770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-158
• Domain position: 73
• Structural Position: 154
• Q(SASA): 0.1036
• 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
Y/H	None	None	1.0	D	0.805	0.877	0.846827325628	gnomAD-4.0.0	1.65241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.51529E-05	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
Y/A	0.999	likely_pathogenic	0.9985	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/C	0.9731	likely_pathogenic	0.973	pathogenic	-1.815	Destabilizing	1.0	D	0.878	deleterious	D	0.662870657	None	None	N
Y/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.662870657	None	None	N
Y/E	0.9998	likely_pathogenic	0.9996	pathogenic	-2.915	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.3014	likely_benign	0.3719	ambiguous	-0.844	Destabilizing	1.0	D	0.693	prob.neutral	D	0.578525244	None	None	N
Y/G	0.9979	likely_pathogenic	0.9965	pathogenic	-2.859	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/H	0.9919	likely_pathogenic	0.9916	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.646447688	None	None	N
Y/I	0.9649	likely_pathogenic	0.9607	pathogenic	-0.887	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/K	0.9998	likely_pathogenic	0.9995	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.9081	likely_pathogenic	0.8991	pathogenic	-0.887	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/M	0.9916	likely_pathogenic	0.9909	pathogenic	-0.957	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/N	0.9972	likely_pathogenic	0.9958	pathogenic	-3.135	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.662870657	None	None	N
Y/P	0.9994	likely_pathogenic	0.999	pathogenic	-1.408	Destabilizing	1.0	D	0.916	deleterious	None	None	None	None	N
Y/Q	0.9997	likely_pathogenic	0.9995	pathogenic	-2.668	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/R	0.9987	likely_pathogenic	0.9978	pathogenic	-2.408	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/S	0.997	likely_pathogenic	0.9957	pathogenic	-3.422	Highly Destabilizing	1.0	D	0.904	deleterious	D	0.662870657	None	None	N
Y/T	0.9987	likely_pathogenic	0.9979	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/V	0.9603	likely_pathogenic	0.9578	pathogenic	-1.408	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/W	0.8251	likely_pathogenic	0.8606	pathogenic	-0.225	Destabilizing	1.0	D	0.796	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.