TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15494	46705;46706;46707	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
N2AB	13853	41782;41783;41784	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
N2A	12926	39001;39002;39003	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
N2B	6429	19510;19511;19512	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
Novex-1	6554	19885;19886;19887	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
Novex-2	6621	20086;20087;20088	chr2:178619837;178619836;178619835	chr2:179484564;179484563;179484562
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-107
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.4
• 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	rs1433448268	-0.054	1.0	D	0.812	0.798	0.929971040554	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
G/V	rs1433448268	-0.054	1.0	D	0.812	0.798	0.929971040554	gnomAD-4.0.0	1.59492E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86454E-06	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	0.4363	ambiguous	0.4113	ambiguous	-0.584	Destabilizing	1.0	D	0.749	deleterious	D	0.597559635	None	None	N
G/C	0.6341	likely_pathogenic	0.6145	pathogenic	-0.915	Destabilizing	1.0	D	0.82	deleterious	D	0.636383633	None	None	N
G/D	0.5315	ambiguous	0.5113	ambiguous	-1.042	Destabilizing	1.0	D	0.839	deleterious	D	0.575643878	None	None	N
G/E	0.5456	ambiguous	0.5189	ambiguous	-1.192	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/F	0.9006	likely_pathogenic	0.8872	pathogenic	-1.243	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
G/H	0.7049	likely_pathogenic	0.6835	pathogenic	-0.906	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/I	0.917	likely_pathogenic	0.8932	pathogenic	-0.591	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/K	0.722	likely_pathogenic	0.7107	pathogenic	-1.138	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/L	0.8419	likely_pathogenic	0.8225	pathogenic	-0.591	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/M	0.8642	likely_pathogenic	0.8478	pathogenic	-0.433	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/N	0.5104	ambiguous	0.5116	ambiguous	-0.761	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/P	0.9891	likely_pathogenic	0.9867	pathogenic	-0.553	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/Q	0.614	likely_pathogenic	0.6016	pathogenic	-1.078	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/R	0.5888	likely_pathogenic	0.5735	pathogenic	-0.614	Destabilizing	1.0	D	0.857	deleterious	D	0.636852509	None	None	N
G/S	0.2753	likely_benign	0.2593	benign	-0.902	Destabilizing	1.0	D	0.795	deleterious	D	0.597668545	None	None	N
G/T	0.5647	likely_pathogenic	0.5388	ambiguous	-0.988	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/V	0.8143	likely_pathogenic	0.7727	pathogenic	-0.553	Destabilizing	1.0	D	0.812	deleterious	D	0.636569435	None	None	N
G/W	0.8445	likely_pathogenic	0.8069	pathogenic	-1.421	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/Y	0.8256	likely_pathogenic	0.7999	pathogenic	-1.081	Destabilizing	1.0	D	0.829	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.