TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8976	27151;27152;27153	chr2:178713208;178713207;178713206	chr2:179577935;179577934;179577933
N2AB	8659	26200;26201;26202	chr2:178713208;178713207;178713206	chr2:179577935;179577934;179577933
N2A	7732	23419;23420;23421	chr2:178713208;178713207;178713206	chr2:179577935;179577934;179577933
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-75
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.4778
• 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
L/P	rs1470719123	-0.425	0.988	N	0.583	0.532	0.809640320441	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1470719123	-0.425	0.988	N	0.583	0.532	0.809640320441	gnomAD-4.0.0	6.57177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	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
L/A	0.4102	ambiguous	0.4424	ambiguous	-1.09	Destabilizing	0.17	N	0.356	neutral	None	None	None	None	N
L/C	0.5699	likely_pathogenic	0.6066	pathogenic	-0.692	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	N
L/D	0.8553	likely_pathogenic	0.877	pathogenic	-0.716	Destabilizing	0.991	D	0.589	neutral	None	None	None	None	N
L/E	0.5543	ambiguous	0.5884	pathogenic	-0.803	Destabilizing	0.991	D	0.578	neutral	None	None	None	None	N
L/F	0.1022	likely_benign	0.1102	benign	-1.157	Destabilizing	0.046	N	0.237	neutral	None	None	None	None	N
L/G	0.7443	likely_pathogenic	0.7756	pathogenic	-1.296	Destabilizing	0.939	D	0.547	neutral	None	None	None	None	N
L/H	0.2867	likely_benign	0.3072	benign	-0.708	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
L/I	0.0974	likely_benign	0.1064	benign	-0.65	Destabilizing	0.759	D	0.411	neutral	None	None	None	None	N
L/K	0.4534	ambiguous	0.494	ambiguous	-0.609	Destabilizing	0.991	D	0.555	neutral	None	None	None	None	N
L/M	0.1112	likely_benign	0.1215	benign	-0.382	Destabilizing	0.988	D	0.523	neutral	N	0.492519643	None	None	N
L/N	0.5926	likely_pathogenic	0.6393	pathogenic	-0.341	Destabilizing	0.997	D	0.58	neutral	None	None	None	None	N
L/P	0.8079	likely_pathogenic	0.8315	pathogenic	-0.764	Destabilizing	0.988	D	0.583	neutral	N	0.465218399	None	None	N
L/Q	0.2433	likely_benign	0.2543	benign	-0.631	Destabilizing	0.996	D	0.576	neutral	N	0.474048526	None	None	N
L/R	0.2995	likely_benign	0.312	benign	-0.014	Destabilizing	0.988	D	0.581	neutral	N	0.464351607	None	None	N
L/S	0.4393	ambiguous	0.4862	ambiguous	-0.816	Destabilizing	0.884	D	0.548	neutral	None	None	None	None	N
L/T	0.3706	ambiguous	0.4077	ambiguous	-0.796	Destabilizing	0.939	D	0.471	neutral	None	None	None	None	N
L/V	0.0959	likely_benign	0.1025	benign	-0.764	Destabilizing	0.134	N	0.244	neutral	N	0.456230769	None	None	N
L/W	0.2425	likely_benign	0.2604	benign	-1.175	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
L/Y	0.3346	likely_benign	0.3542	ambiguous	-0.903	Destabilizing	0.964	D	0.483	neutral	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.