TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22571	67936;67937;67938	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
N2AB	20930	63013;63014;63015	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
N2A	20003	60232;60233;60234	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
N2B	13506	40741;40742;40743	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
Novex-1	13631	41116;41117;41118	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
Novex-2	13698	41317;41318;41319	chr2:178579319;178579318;178579317	chr2:179444046;179444045;179444044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-127
• Domain position: 12
• Structural Position: 31
• Q(SASA): 0.5269
• Predicted PPI site: I

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
K/M	None	None	1.0	N	0.581	0.589	0.488477830397	gnomAD-4.0.0	1.60181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43724E-05	0
K/N	None	None	0.122	N	0.251	0.17	0.210429274316	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.5363	ambiguous	0.4541	ambiguous	-0.346	Destabilizing	0.985	D	0.508	neutral	None	None	None	None	I
K/C	0.7783	likely_pathogenic	0.7448	pathogenic	-0.406	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
K/D	0.692	likely_pathogenic	0.6242	pathogenic	-0.086	Destabilizing	0.942	D	0.499	neutral	None	None	None	None	I
K/E	0.3509	ambiguous	0.2864	benign	-0.014	Destabilizing	0.961	D	0.48	neutral	N	0.456481486	None	None	I
K/F	0.8933	likely_pathogenic	0.8502	pathogenic	-0.191	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	I
K/G	0.7072	likely_pathogenic	0.6388	pathogenic	-0.67	Destabilizing	0.97	D	0.518	neutral	None	None	None	None	I
K/H	0.342	ambiguous	0.3167	benign	-1.082	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	I
K/I	0.5089	ambiguous	0.4169	ambiguous	0.468	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	I
K/L	0.5337	ambiguous	0.4575	ambiguous	0.468	Stabilizing	0.985	D	0.5	neutral	None	None	None	None	I
K/M	0.3537	ambiguous	0.2845	benign	0.335	Stabilizing	1.0	D	0.581	neutral	N	0.495976359	None	None	I
K/N	0.4962	ambiguous	0.4269	ambiguous	-0.266	Destabilizing	0.122	N	0.251	neutral	N	0.46829599	None	None	I
K/P	0.788	likely_pathogenic	0.7638	pathogenic	0.228	Stabilizing	0.999	D	0.571	neutral	None	None	None	None	I
K/Q	0.1736	likely_benign	0.1537	benign	-0.379	Destabilizing	0.994	D	0.491	neutral	N	0.499888333	None	None	I
K/R	0.1009	likely_benign	0.1024	benign	-0.545	Destabilizing	0.98	D	0.437	neutral	N	0.511625479	None	None	I
K/S	0.5478	ambiguous	0.4678	ambiguous	-0.844	Destabilizing	0.97	D	0.466	neutral	None	None	None	None	I
K/T	0.244	likely_benign	0.1847	benign	-0.582	Destabilizing	0.961	D	0.523	neutral	N	0.478184909	None	None	I
K/V	0.4477	ambiguous	0.3692	ambiguous	0.228	Stabilizing	0.999	D	0.527	neutral	None	None	None	None	I
K/W	0.863	likely_pathogenic	0.8385	pathogenic	-0.103	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/Y	0.769	likely_pathogenic	0.7162	pathogenic	0.196	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	I

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.