TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20850	62773;62774;62775	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
N2AB	19209	57850;57851;57852	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
N2A	18282	55069;55070;55071	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
N2B	11785	35578;35579;35580	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
Novex-1	11910	35953;35954;35955	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
Novex-2	11977	36154;36155;36156	chr2:178589177;178589176;178589175	chr2:179453904;179453903;179453902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-122
• Domain position: 82
• Structural Position: 163
• Q(SASA): 0.5297
• 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
A/V	rs2049701405	None	0.085	N	0.478	0.193	0.29527378943	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
A/V	rs2049701405	None	0.085	N	0.478	0.193	0.29527378943	gnomAD-4.0.0	6.57583E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.06954E-04	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
A/C	0.6072	likely_pathogenic	0.6311	pathogenic	-0.865	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	I
A/D	0.9043	likely_pathogenic	0.9117	pathogenic	-0.595	Destabilizing	0.996	D	0.728	prob.delet.	N	0.518488387	None	None	I
A/E	0.8168	likely_pathogenic	0.8414	pathogenic	-0.751	Destabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	I
A/F	0.6327	likely_pathogenic	0.6322	pathogenic	-0.951	Destabilizing	0.983	D	0.756	deleterious	None	None	None	None	I
A/G	0.3362	likely_benign	0.3207	benign	-0.272	Destabilizing	0.963	D	0.633	neutral	N	0.484531149	None	None	I
A/H	0.8066	likely_pathogenic	0.8231	pathogenic	-0.236	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
A/I	0.4875	ambiguous	0.5253	ambiguous	-0.448	Destabilizing	0.745	D	0.627	neutral	None	None	None	None	I
A/K	0.9316	likely_pathogenic	0.9378	pathogenic	-0.597	Destabilizing	0.992	D	0.7	prob.neutral	None	None	None	None	I
A/L	0.4553	ambiguous	0.4631	ambiguous	-0.448	Destabilizing	0.895	D	0.567	neutral	None	None	None	None	I
A/M	0.4433	ambiguous	0.4858	ambiguous	-0.556	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	I
A/N	0.6871	likely_pathogenic	0.7204	pathogenic	-0.311	Destabilizing	0.997	D	0.754	deleterious	None	None	None	None	I
A/P	0.9503	likely_pathogenic	0.9426	pathogenic	-0.361	Destabilizing	0.996	D	0.711	prob.delet.	D	0.530009277	None	None	I
A/Q	0.7488	likely_pathogenic	0.7689	pathogenic	-0.594	Destabilizing	0.997	D	0.722	prob.delet.	None	None	None	None	I
A/R	0.8785	likely_pathogenic	0.878	pathogenic	-0.124	Destabilizing	0.992	D	0.72	prob.delet.	None	None	None	None	I
A/S	0.1479	likely_benign	0.1526	benign	-0.487	Destabilizing	0.928	D	0.633	neutral	N	0.463834319	None	None	I
A/T	0.2061	likely_benign	0.2143	benign	-0.572	Destabilizing	0.928	D	0.666	neutral	N	0.490505403	None	None	I
A/V	0.2128	likely_benign	0.2306	benign	-0.361	Destabilizing	0.085	N	0.478	neutral	N	0.483996161	None	None	I
A/W	0.9524	likely_pathogenic	0.9455	pathogenic	-1.043	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	I
A/Y	0.8004	likely_pathogenic	0.8166	pathogenic	-0.73	Destabilizing	0.992	D	0.759	deleterious	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.