TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26786	80581;80582;80583	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
N2AB	25145	75658;75659;75660	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
N2A	24218	72877;72878;72879	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
N2B	17721	53386;53387;53388	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
Novex-1	17846	53761;53762;53763	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
Novex-2	17913	53962;53963;53964	chr2:178565776;178565775;178565774	chr2:179430503;179430502;179430501
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: Fn3-83
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6837
• 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/N	rs530566362	0.3	1.0	N	0.733	0.198	0.146414634003	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None

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	0.6787	likely_pathogenic	0.621	pathogenic	-0.02	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
K/C	0.8902	likely_pathogenic	0.8842	pathogenic	-0.293	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
K/D	0.8049	likely_pathogenic	0.7576	pathogenic	0.036	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
K/E	0.5214	ambiguous	0.4384	ambiguous	0.046	Stabilizing	0.995	D	0.635	neutral	N	0.512264905	None	None	I
K/F	0.9178	likely_pathogenic	0.8992	pathogenic	-0.189	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/G	0.7959	likely_pathogenic	0.7451	pathogenic	-0.229	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
K/H	0.5239	ambiguous	0.5003	ambiguous	-0.473	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
K/I	0.6298	likely_pathogenic	0.6011	pathogenic	0.452	Stabilizing	0.989	D	0.729	prob.delet.	None	None	None	None	I
K/L	0.6502	likely_pathogenic	0.6037	pathogenic	0.452	Stabilizing	0.989	D	0.675	prob.neutral	None	None	None	None	I
K/M	0.4841	ambiguous	0.4442	ambiguous	0.228	Stabilizing	0.999	D	0.69	prob.neutral	N	0.513382413	None	None	I
K/N	0.6907	likely_pathogenic	0.6116	pathogenic	0.122	Stabilizing	1.0	D	0.733	prob.delet.	N	0.448613285	None	None	I
K/P	0.8421	likely_pathogenic	0.8061	pathogenic	0.323	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
K/Q	0.3348	likely_benign	0.2947	benign	-0.06	Destabilizing	0.997	D	0.716	prob.delet.	N	0.502298628	None	None	I
K/R	0.1007	likely_benign	0.0992	benign	-0.084	Destabilizing	0.992	D	0.611	neutral	N	0.49681545	None	None	I
K/S	0.7372	likely_pathogenic	0.6711	pathogenic	-0.38	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
K/T	0.4423	ambiguous	0.3903	ambiguous	-0.22	Destabilizing	0.999	D	0.725	prob.delet.	N	0.499221037	None	None	I
K/V	0.6056	likely_pathogenic	0.5673	pathogenic	0.323	Stabilizing	0.992	D	0.733	prob.delet.	None	None	None	None	I
K/W	0.8928	likely_pathogenic	0.8932	pathogenic	-0.183	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
K/Y	0.8144	likely_pathogenic	0.7995	pathogenic	0.163	Stabilizing	0.998	D	0.737	prob.delet.	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.