TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32533	97822;97823;97824	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
N2AB	30892	92899;92900;92901	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
N2A	29965	90118;90119;90120	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
N2B	23468	70627;70628;70629	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
Novex-1	23593	71002;71003;71004	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
Novex-2	23660	71203;71204;71205	chr2:178541480;178541479;178541478	chr2:179406207;179406206;179406205
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: Fn3-125
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0702
• 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	0.88	0.662	0.82113241323	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85976E-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	0.5543	ambiguous	0.5068	ambiguous	-0.546	Destabilizing	1.0	D	0.588	neutral	N	0.496139446	None	None	N
G/C	0.7677	likely_pathogenic	0.7904	pathogenic	-0.817	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/D	0.9469	likely_pathogenic	0.9546	pathogenic	-1.142	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
G/E	0.9595	likely_pathogenic	0.9669	pathogenic	-1.121	Destabilizing	1.0	D	0.878	deleterious	N	0.485592835	None	None	N
G/F	0.986	likely_pathogenic	0.9866	pathogenic	-0.692	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/H	0.9587	likely_pathogenic	0.9668	pathogenic	-1.392	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/I	0.9836	likely_pathogenic	0.9841	pathogenic	0.085	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/K	0.9855	likely_pathogenic	0.9873	pathogenic	-1.084	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/L	0.9815	likely_pathogenic	0.9807	pathogenic	0.085	Stabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/M	0.981	likely_pathogenic	0.9814	pathogenic	-0.04	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/N	0.8854	likely_pathogenic	0.9196	pathogenic	-0.925	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
G/P	0.9994	likely_pathogenic	0.9994	pathogenic	-0.081	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
G/Q	0.9502	likely_pathogenic	0.9578	pathogenic	-0.964	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/R	0.9459	likely_pathogenic	0.9494	pathogenic	-0.988	Destabilizing	1.0	D	0.869	deleterious	N	0.49002338	None	None	N
G/S	0.4074	ambiguous	0.4181	ambiguous	-1.244	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/T	0.8927	likely_pathogenic	0.8938	pathogenic	-1.127	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/V	0.9601	likely_pathogenic	0.9594	pathogenic	-0.081	Destabilizing	1.0	D	0.88	deleterious	D	0.533677856	None	None	N
G/W	0.9659	likely_pathogenic	0.9691	pathogenic	-1.241	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/Y	0.9581	likely_pathogenic	0.9648	pathogenic	-0.718	Destabilizing	1.0	D	0.841	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.