TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14806	44641;44642;44643	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
N2AB	13165	39718;39719;39720	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
N2A	12238	36937;36938;36939	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
N2B	5741	17446;17447;17448	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
Novex-1	5866	17821;17822;17823	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
Novex-2	5933	18022;18023;18024	chr2:178629309;178629308;178629307	chr2:179494036;179494035;179494034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-99
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.2081
• 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
S/T	rs778340859	-0.225	0.124	N	0.459	0.092	0.0986583533028	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	1.13289E-04	None	0	None	0	0	0
S/T	rs778340859	-0.225	0.124	N	0.459	0.092	0.0986583533028	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94401E-04	None	0	0	0	0	0
S/T	rs778340859	-0.225	0.124	N	0.459	0.092	0.0986583533028	gnomAD-4.0.0	2.56689E-06	None	None	None	None	N	None	0	0	None	0	4.88257E-05	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
S/A	0.156	likely_benign	0.1594	benign	-0.189	Destabilizing	0.072	N	0.456	neutral	None	None	None	None	N
S/C	0.1577	likely_benign	0.1591	benign	-0.324	Destabilizing	0.958	D	0.447	neutral	N	0.496220995	None	None	N
S/D	0.3443	ambiguous	0.3803	ambiguous	0.123	Stabilizing	0.157	N	0.392	neutral	None	None	None	None	N
S/E	0.625	likely_pathogenic	0.712	pathogenic	0.034	Stabilizing	0.157	N	0.397	neutral	None	None	None	None	N
S/F	0.4816	ambiguous	0.5543	ambiguous	-0.787	Destabilizing	0.89	D	0.511	neutral	None	None	None	None	N
S/G	0.0745	likely_benign	0.0793	benign	-0.298	Destabilizing	None	N	0.198	neutral	N	0.451618433	None	None	N
S/H	0.503	ambiguous	0.5328	ambiguous	-0.736	Destabilizing	0.832	D	0.397	neutral	None	None	None	None	N
S/I	0.3952	ambiguous	0.4357	ambiguous	-0.037	Destabilizing	0.667	D	0.494	neutral	D	0.600305519	None	None	N
S/K	0.7406	likely_pathogenic	0.8051	pathogenic	-0.504	Destabilizing	0.157	N	0.405	neutral	None	None	None	None	N
S/L	0.2018	likely_benign	0.2129	benign	-0.037	Destabilizing	0.567	D	0.447	neutral	None	None	None	None	N
S/M	0.3676	ambiguous	0.3794	ambiguous	-0.013	Destabilizing	0.968	D	0.425	neutral	None	None	None	None	N
S/N	0.1662	likely_benign	0.1553	benign	-0.265	Destabilizing	0.001	N	0.285	neutral	N	0.455931914	None	None	N
S/P	0.7878	likely_pathogenic	0.7857	pathogenic	-0.058	Destabilizing	0.726	D	0.365	neutral	None	None	None	None	N
S/Q	0.6777	likely_pathogenic	0.7239	pathogenic	-0.458	Destabilizing	0.567	D	0.376	neutral	None	None	None	None	N
S/R	0.6755	likely_pathogenic	0.7508	pathogenic	-0.294	Destabilizing	0.715	D	0.375	neutral	D	0.598276693	None	None	N
S/T	0.0972	likely_benign	0.0922	benign	-0.33	Destabilizing	0.124	N	0.459	neutral	N	0.446436766	None	None	N
S/V	0.3736	ambiguous	0.3901	ambiguous	-0.058	Destabilizing	0.726	D	0.449	neutral	None	None	None	None	N
S/W	0.5883	likely_pathogenic	0.6657	pathogenic	-0.865	Destabilizing	0.968	D	0.649	neutral	None	None	None	None	N
S/Y	0.423	ambiguous	0.4971	ambiguous	-0.558	Destabilizing	0.89	D	0.512	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.