TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31673	95242;95243;95244	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
N2AB	30032	90319;90320;90321	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
N2A	29105	87538;87539;87540	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
N2B	22608	68047;68048;68049	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
Novex-1	22733	68422;68423;68424	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
Novex-2	22800	68623;68624;68625	chr2:178546314;178546313;178546312	chr2:179411041;179411040;179411039
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-152
• Domain position: 53
• Structural Position: 138
• Q(SASA): 0.1528
• 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
A/V	rs200920551	None	0.996	N	0.68	0.422	0.336892272479	gnomAD-4.0.0	4.77373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71661E-06	0	3.02425E-05

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	0.591	likely_pathogenic	0.5794	pathogenic	-1.231	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/D	0.9972	likely_pathogenic	0.9974	pathogenic	-2.584	Highly Destabilizing	0.999	D	0.853	deleterious	N	0.481816207	None	None	N
A/E	0.9901	likely_pathogenic	0.9904	pathogenic	-2.301	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/F	0.898	likely_pathogenic	0.91	pathogenic	-0.645	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/G	0.4613	ambiguous	0.4683	ambiguous	-1.734	Destabilizing	0.998	D	0.687	prob.neutral	N	0.481816207	None	None	N
A/H	0.9931	likely_pathogenic	0.9932	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/I	0.4777	ambiguous	0.5168	ambiguous	0.444	Stabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
A/K	0.9967	likely_pathogenic	0.9967	pathogenic	-1.353	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/L	0.3001	likely_benign	0.3289	benign	0.444	Stabilizing	0.997	D	0.69	prob.neutral	None	None	None	None	N
A/M	0.4698	ambiguous	0.5009	ambiguous	0.108	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/N	0.9864	likely_pathogenic	0.9877	pathogenic	-1.873	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/P	0.9953	likely_pathogenic	0.9955	pathogenic	-0.045	Destabilizing	1.0	D	0.791	deleterious	N	0.481816207	None	None	N
A/Q	0.9837	likely_pathogenic	0.9839	pathogenic	-1.509	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/R	0.9905	likely_pathogenic	0.9901	pathogenic	-1.654	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/S	0.5377	ambiguous	0.5458	ambiguous	-2.302	Highly Destabilizing	0.992	D	0.689	prob.neutral	N	0.481816207	None	None	N
A/T	0.3514	ambiguous	0.3706	ambiguous	-1.861	Destabilizing	0.884	D	0.491	neutral	N	0.452186734	None	None	N
A/V	0.1917	likely_benign	0.2093	benign	-0.045	Destabilizing	0.996	D	0.68	prob.neutral	N	0.409318604	None	None	N
A/W	0.9949	likely_pathogenic	0.9952	pathogenic	-1.55	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/Y	0.9755	likely_pathogenic	0.9769	pathogenic	-0.937	Destabilizing	1.0	D	0.852	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.