TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23576	70951;70952;70953	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
N2AB	21935	66028;66029;66030	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
N2A	21008	63247;63248;63249	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
N2B	14511	43756;43757;43758	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
Novex-1	14636	44131;44132;44133	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
Novex-2	14703	44332;44333;44334	chr2:178575406;178575405;178575404	chr2:179440133;179440132;179440131
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-59
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2964
• 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/F	None	None	0.995	N	0.525	0.489	0.527557778142	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	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	0.0951	likely_benign	0.0928	benign	-0.334	Destabilizing	0.002	N	0.273	neutral	N	0.466733976	None	None	N
S/C	0.1252	likely_benign	0.1171	benign	-0.261	Destabilizing	0.995	D	0.457	neutral	D	0.525454513	None	None	N
S/D	0.5082	ambiguous	0.4461	ambiguous	-0.081	Destabilizing	0.914	D	0.357	neutral	None	None	None	None	N
S/E	0.5802	likely_pathogenic	0.5131	ambiguous	-0.191	Destabilizing	0.937	D	0.356	neutral	None	None	None	None	N
S/F	0.2572	likely_benign	0.2307	benign	-0.982	Destabilizing	0.995	D	0.525	neutral	N	0.495740463	None	None	N
S/G	0.1102	likely_benign	0.1008	benign	-0.413	Destabilizing	0.908	D	0.387	neutral	None	None	None	None	N
S/H	0.4256	ambiguous	0.3679	ambiguous	-0.924	Destabilizing	1.0	D	0.45	neutral	None	None	None	None	N
S/I	0.2416	likely_benign	0.1973	benign	-0.255	Destabilizing	0.993	D	0.485	neutral	None	None	None	None	N
S/K	0.6752	likely_pathogenic	0.6087	pathogenic	-0.487	Destabilizing	0.975	D	0.362	neutral	None	None	None	None	N
S/L	0.097	likely_benign	0.0911	benign	-0.255	Destabilizing	0.952	D	0.392	neutral	None	None	None	None	N
S/M	0.1752	likely_benign	0.166	benign	0.044	Stabilizing	1.0	D	0.441	neutral	None	None	None	None	N
S/N	0.1808	likely_benign	0.149	benign	-0.163	Destabilizing	0.554	D	0.41	neutral	None	None	None	None	N
S/P	0.7504	likely_pathogenic	0.7024	pathogenic	-0.255	Destabilizing	0.983	D	0.409	neutral	N	0.466747202	None	None	N
S/Q	0.5327	ambiguous	0.4756	ambiguous	-0.475	Destabilizing	0.996	D	0.389	neutral	None	None	None	None	N
S/R	0.6405	likely_pathogenic	0.5627	ambiguous	-0.228	Destabilizing	0.996	D	0.413	neutral	None	None	None	None	N
S/T	0.0741	likely_benign	0.0732	benign	-0.278	Destabilizing	0.005	N	0.233	neutral	N	0.461721442	None	None	N
S/V	0.2056	likely_benign	0.1827	benign	-0.255	Destabilizing	0.881	D	0.416	neutral	None	None	None	None	N
S/W	0.3955	ambiguous	0.355	ambiguous	-0.989	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
S/Y	0.2603	likely_benign	0.2275	benign	-0.714	Destabilizing	0.998	D	0.533	neutral	N	0.507096769	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.