TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7244	21955;21956;21957	chr2:178723277;178723276;178723275	chr2:179588004;179588003;179588002
N2AB	6927	21004;21005;21006	chr2:178723277;178723276;178723275	chr2:179588004;179588003;179588002
N2A	6000	18223;18224;18225	chr2:178723277;178723276;178723275	chr2:179588004;179588003;179588002
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-57
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.4074
• 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
G/E	None	None	1.0	D	0.775	0.623	0.848142195229	gnomAD-4.0.0	5.47479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49792E-06	0	4.97133E-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
G/A	0.3823	ambiguous	0.378	ambiguous	-0.372	Destabilizing	0.999	D	0.661	neutral	D	0.653543042	None	None	N
G/C	0.5678	likely_pathogenic	0.5785	pathogenic	-0.908	Destabilizing	0.964	D	0.695	prob.neutral	None	None	None	None	N
G/D	0.3276	likely_benign	0.3425	ambiguous	-0.521	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/E	0.2741	likely_benign	0.2869	benign	-0.683	Destabilizing	1.0	D	0.775	deleterious	D	0.606858305	None	None	N
G/F	0.8298	likely_pathogenic	0.8129	pathogenic	-1.128	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/H	0.5842	likely_pathogenic	0.5967	pathogenic	-0.615	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/I	0.8018	likely_pathogenic	0.7832	pathogenic	-0.509	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/K	0.5121	ambiguous	0.5408	ambiguous	-0.726	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/L	0.7307	likely_pathogenic	0.7062	pathogenic	-0.509	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
G/M	0.7646	likely_pathogenic	0.7516	pathogenic	-0.437	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/N	0.3916	ambiguous	0.3958	ambiguous	-0.409	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/P	0.9755	likely_pathogenic	0.9712	pathogenic	-0.431	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/Q	0.3843	ambiguous	0.4001	ambiguous	-0.713	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/R	0.369	ambiguous	0.3918	ambiguous	-0.302	Destabilizing	1.0	D	0.786	deleterious	D	0.628206735	None	None	N
G/S	0.1997	likely_benign	0.2042	benign	-0.582	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/T	0.4566	ambiguous	0.4386	ambiguous	-0.674	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/V	0.6705	likely_pathogenic	0.6507	pathogenic	-0.431	Destabilizing	1.0	D	0.739	prob.delet.	D	0.637695125	None	None	N
G/W	0.6782	likely_pathogenic	0.6585	pathogenic	-1.251	Destabilizing	1.0	D	0.763	deleterious	D	0.654148455	None	None	N
G/Y	0.7204	likely_pathogenic	0.7234	pathogenic	-0.901	Destabilizing	1.0	D	0.785	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.