TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22408	67447;67448;67449	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
N2AB	20767	62524;62525;62526	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
N2A	19840	59743;59744;59745	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
N2B	13343	40252;40253;40254	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
Novex-1	13468	40627;40628;40629	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
Novex-2	13535	40828;40829;40830	chr2:178580065;178580064;178580063	chr2:179444792;179444791;179444790
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-50
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.0987
• 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
C/R	None	None	0.97	N	0.779	0.56	0.806097659105	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	2.77531E-05	None	0	0	0	0	0
C/S	None	None	0.904	N	0.646	0.443	0.589282225109	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	5.66636E-05	0	None	0	0	None	0	0	0	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
C/A	0.7951	likely_pathogenic	0.8099	pathogenic	-1.569	Destabilizing	0.717	D	0.598	neutral	None	None	None	None	N
C/D	0.981	likely_pathogenic	0.9863	pathogenic	-0.52	Destabilizing	0.993	D	0.759	deleterious	None	None	None	None	N
C/E	0.9879	likely_pathogenic	0.9907	pathogenic	-0.329	Destabilizing	0.978	D	0.769	deleterious	None	None	None	None	N
C/F	0.8021	likely_pathogenic	0.7976	pathogenic	-1.069	Destabilizing	0.89	D	0.665	neutral	N	0.489446586	None	None	N
C/G	0.6894	likely_pathogenic	0.7452	pathogenic	-1.912	Destabilizing	0.97	D	0.727	prob.delet.	N	0.517398579	None	None	N
C/H	0.9591	likely_pathogenic	0.9663	pathogenic	-2.136	Highly Destabilizing	0.988	D	0.773	deleterious	None	None	None	None	N
C/I	0.7659	likely_pathogenic	0.6649	pathogenic	-0.659	Destabilizing	0.956	D	0.654	neutral	None	None	None	None	N
C/K	0.9937	likely_pathogenic	0.9948	pathogenic	-0.516	Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
C/L	0.84	likely_pathogenic	0.7919	pathogenic	-0.659	Destabilizing	0.754	D	0.569	neutral	None	None	None	None	N
C/M	0.8873	likely_pathogenic	0.8668	pathogenic	0.081	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	N
C/N	0.8307	likely_pathogenic	0.8694	pathogenic	-0.899	Destabilizing	0.978	D	0.773	deleterious	None	None	None	None	N
C/P	0.9859	likely_pathogenic	0.9889	pathogenic	-0.938	Destabilizing	0.993	D	0.778	deleterious	None	None	None	None	N
C/Q	0.9732	likely_pathogenic	0.9788	pathogenic	-0.549	Destabilizing	0.978	D	0.777	deleterious	None	None	None	None	N
C/R	0.9714	likely_pathogenic	0.9771	pathogenic	-0.903	Destabilizing	0.97	D	0.779	deleterious	N	0.500746304	None	None	N
C/S	0.7294	likely_pathogenic	0.7815	pathogenic	-1.31	Destabilizing	0.904	D	0.646	neutral	N	0.472908813	None	None	N
C/T	0.8137	likely_pathogenic	0.8042	pathogenic	-0.915	Destabilizing	0.978	D	0.665	neutral	None	None	None	None	N
C/V	0.6408	likely_pathogenic	0.5255	ambiguous	-0.938	Destabilizing	0.86	D	0.63	neutral	None	None	None	None	N
C/W	0.956	likely_pathogenic	0.9604	pathogenic	-1.269	Destabilizing	0.992	D	0.691	prob.neutral	D	0.528275216	None	None	N
C/Y	0.869	likely_pathogenic	0.8793	pathogenic	-1.102	Destabilizing	0.014	N	0.521	neutral	N	0.477672207	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.