TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5998	18217;18218;18219	chr2:178730541;178730540;178730539	chr2:179595268;179595267;179595266
N2AB	5681	17266;17267;17268	chr2:178730541;178730540;178730539	chr2:179595268;179595267;179595266
N2A	4754	14485;14486;14487	chr2:178730541;178730540;178730539	chr2:179595268;179595267;179595266
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-43
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2398
• 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
G/R	rs757934638	-0.236	1.0	D	0.877	0.627	0.873637900166	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
G/R	rs757934638	-0.236	1.0	D	0.877	0.627	0.873637900166	gnomAD-4.0.0	1.36888E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99755E-07	0	1.65733E-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	0.8944	likely_pathogenic	0.909	pathogenic	-0.451	Destabilizing	1.0	D	0.751	deleterious	D	0.596425204	None	None	I
G/C	0.9768	likely_pathogenic	0.9812	pathogenic	-0.754	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/D	0.9741	likely_pathogenic	0.9818	pathogenic	-1.246	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/E	0.9867	likely_pathogenic	0.9902	pathogenic	-1.427	Destabilizing	1.0	D	0.848	deleterious	D	0.550616109	None	None	I
G/F	0.993	likely_pathogenic	0.9944	pathogenic	-1.285	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
G/H	0.9918	likely_pathogenic	0.9942	pathogenic	-0.808	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/I	0.9939	likely_pathogenic	0.9953	pathogenic	-0.614	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/K	0.9912	likely_pathogenic	0.9935	pathogenic	-1.102	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
G/L	0.9918	likely_pathogenic	0.9933	pathogenic	-0.614	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/M	0.9949	likely_pathogenic	0.9957	pathogenic	-0.422	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/N	0.9777	likely_pathogenic	0.9836	pathogenic	-0.629	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/P	0.9993	likely_pathogenic	0.9995	pathogenic	-0.528	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/Q	0.9824	likely_pathogenic	0.9871	pathogenic	-1.001	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/R	0.9696	likely_pathogenic	0.9782	pathogenic	-0.532	Destabilizing	1.0	D	0.877	deleterious	D	0.628897895	None	None	I
G/S	0.8131	likely_pathogenic	0.8512	pathogenic	-0.649	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/T	0.9763	likely_pathogenic	0.981	pathogenic	-0.788	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/V	0.9867	likely_pathogenic	0.9898	pathogenic	-0.528	Destabilizing	1.0	D	0.846	deleterious	D	0.654809255	None	None	I
G/W	0.9877	likely_pathogenic	0.9917	pathogenic	-1.437	Destabilizing	1.0	D	0.819	deleterious	D	0.655212863	None	None	I
G/Y	0.9915	likely_pathogenic	0.9937	pathogenic	-1.12	Destabilizing	1.0	D	0.846	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.