TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7968	24127;24128;24129	chr2:178719590;178719589;178719588	chr2:179584317;179584316;179584315
N2AB	7651	23176;23177;23178	chr2:178719590;178719589;178719588	chr2:179584317;179584316;179584315
N2A	6724	20395;20396;20397	chr2:178719590;178719589;178719588	chr2:179584317;179584316;179584315
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: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-64
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.2621
• 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/V	None	None	1.0	D	0.807	0.618	0.911182896716	gnomAD-4.0.0	1.37035E-06	None	None	None	None	N	None	5.98086E-05	0	None	0	0	None	0	0	0	0	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
G/A	0.7965	likely_pathogenic	0.8109	pathogenic	-0.312	Destabilizing	0.998	D	0.596	neutral	D	0.620105999	None	None	N
G/C	0.9373	likely_pathogenic	0.9495	pathogenic	-0.932	Destabilizing	1.0	D	0.763	deleterious	D	0.658695333	None	None	N
G/D	0.9131	likely_pathogenic	0.9248	pathogenic	-0.555	Destabilizing	1.0	D	0.815	deleterious	D	0.597646748	None	None	N
G/E	0.9392	likely_pathogenic	0.9519	pathogenic	-0.723	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/F	0.9868	likely_pathogenic	0.9898	pathogenic	-1.033	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
G/H	0.9846	likely_pathogenic	0.9888	pathogenic	-0.479	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/I	0.9843	likely_pathogenic	0.9875	pathogenic	-0.489	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/K	0.9839	likely_pathogenic	0.9891	pathogenic	-0.773	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/L	0.9774	likely_pathogenic	0.984	pathogenic	-0.489	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/M	0.9864	likely_pathogenic	0.9893	pathogenic	-0.493	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/N	0.9576	likely_pathogenic	0.9641	pathogenic	-0.477	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
G/P	0.9985	likely_pathogenic	0.9987	pathogenic	-0.399	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/Q	0.9541	likely_pathogenic	0.9671	pathogenic	-0.777	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/R	0.9497	likely_pathogenic	0.9667	pathogenic	-0.309	Destabilizing	1.0	D	0.826	deleterious	D	0.620307803	None	None	N
G/S	0.6765	likely_pathogenic	0.6989	pathogenic	-0.626	Destabilizing	0.991	D	0.547	neutral	D	0.581425583	None	None	N
G/T	0.9358	likely_pathogenic	0.9465	pathogenic	-0.725	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/V	0.9676	likely_pathogenic	0.9741	pathogenic	-0.399	Destabilizing	1.0	D	0.807	deleterious	D	0.626253003	None	None	N
G/W	0.9652	likely_pathogenic	0.9719	pathogenic	-1.156	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/Y	0.9776	likely_pathogenic	0.982	pathogenic	-0.821	Destabilizing	1.0	D	0.828	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.