TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6985	21178;21179;21180	chr2:178724422;178724421;178724420	chr2:179589149;179589148;179589147
N2AB	6668	20227;20228;20229	chr2:178724422;178724421;178724420	chr2:179589149;179589148;179589147
N2A	5741	17446;17447;17448	chr2:178724422;178724421;178724420	chr2:179589149;179589148;179589147
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-54
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.4658
• 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	N	0.673	0.427	0.480801007081	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/R	rs1451519377	-0.319	1.0	N	0.699	0.462	0.633723653509	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
G/R	rs1451519377	-0.319	1.0	N	0.699	0.462	0.633723653509	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88274E-05	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	0.4862	ambiguous	0.3846	ambiguous	-0.315	Destabilizing	0.999	D	0.492	neutral	N	0.479127011	None	None	N
G/C	0.6039	likely_pathogenic	0.5811	pathogenic	-0.837	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/D	0.2236	likely_benign	0.2042	benign	-0.532	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
G/E	0.3157	likely_benign	0.2586	benign	-0.685	Destabilizing	1.0	D	0.673	neutral	N	0.51116604	None	None	N
G/F	0.9288	likely_pathogenic	0.8962	pathogenic	-0.978	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/H	0.5644	likely_pathogenic	0.4982	ambiguous	-0.529	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/I	0.8781	likely_pathogenic	0.8354	pathogenic	-0.416	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/K	0.4973	ambiguous	0.4187	ambiguous	-0.84	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
G/L	0.8787	likely_pathogenic	0.8196	pathogenic	-0.416	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/M	0.8593	likely_pathogenic	0.801	pathogenic	-0.514	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/N	0.3164	likely_benign	0.2541	benign	-0.458	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
G/P	0.9936	likely_pathogenic	0.9898	pathogenic	-0.348	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/Q	0.3847	ambiguous	0.3182	benign	-0.729	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/R	0.362	ambiguous	0.3022	benign	-0.388	Destabilizing	1.0	D	0.699	prob.neutral	N	0.474758918	None	None	N
G/S	0.1665	likely_benign	0.1402	benign	-0.617	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
G/T	0.5904	likely_pathogenic	0.4821	ambiguous	-0.698	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
G/V	0.8126	likely_pathogenic	0.7426	pathogenic	-0.348	Destabilizing	0.989	D	0.556	neutral	N	0.500713986	None	None	N
G/W	0.7793	likely_pathogenic	0.754	pathogenic	-1.143	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
G/Y	0.8139	likely_pathogenic	0.7737	pathogenic	-0.794	Destabilizing	1.0	D	0.753	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.