TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20414	61465;61466;61467	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
N2AB	18773	56542;56543;56544	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
N2A	17846	53761;53762;53763	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
N2B	11349	34270;34271;34272	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
Novex-1	11474	34645;34646;34647	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
Novex-2	11541	34846;34847;34848	chr2:178590485;178590484;178590483	chr2:179455212;179455211;179455210
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-36
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.5499
• 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	0.864	N	0.636	0.226	0.484400871567	gnomAD-4.0.0	1.36894E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16012E-05	1.65706E-05

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	0.2091	likely_benign	0.2523	benign	-0.385	Destabilizing	0.645	D	0.389	neutral	N	0.463226986	None	None	N
G/C	0.3616	ambiguous	0.4029	ambiguous	-1.072	Destabilizing	0.993	D	0.698	prob.neutral	N	0.489600127	None	None	N
G/D	0.2045	likely_benign	0.2059	benign	-0.793	Destabilizing	0.006	N	0.374	neutral	N	0.489011539	None	None	N
G/E	0.2468	likely_benign	0.2659	benign	-0.945	Destabilizing	0.547	D	0.469	neutral	None	None	None	None	N
G/F	0.7255	likely_pathogenic	0.76	pathogenic	-1.118	Destabilizing	0.981	D	0.668	neutral	None	None	None	None	N
G/H	0.4875	ambiguous	0.5302	ambiguous	-0.407	Destabilizing	0.985	D	0.607	neutral	None	None	None	None	N
G/I	0.5059	ambiguous	0.5611	ambiguous	-0.635	Destabilizing	0.894	D	0.689	prob.neutral	None	None	None	None	N
G/K	0.5408	ambiguous	0.5752	pathogenic	-0.833	Destabilizing	0.894	D	0.535	neutral	None	None	None	None	N
G/L	0.5942	likely_pathogenic	0.6477	pathogenic	-0.635	Destabilizing	0.894	D	0.669	neutral	None	None	None	None	N
G/M	0.6105	likely_pathogenic	0.6655	pathogenic	-0.799	Destabilizing	0.995	D	0.69	prob.neutral	None	None	None	None	N
G/N	0.2765	likely_benign	0.2975	benign	-0.546	Destabilizing	0.547	D	0.367	neutral	None	None	None	None	N
G/P	0.8897	likely_pathogenic	0.8974	pathogenic	-0.528	Destabilizing	0.945	D	0.587	neutral	None	None	None	None	N
G/Q	0.3862	ambiguous	0.4211	ambiguous	-0.813	Destabilizing	0.894	D	0.585	neutral	None	None	None	None	N
G/R	0.4371	ambiguous	0.4696	ambiguous	-0.378	Destabilizing	0.864	D	0.587	neutral	N	0.46446798	None	None	N
G/S	0.1531	likely_benign	0.1779	benign	-0.678	Destabilizing	0.477	N	0.362	neutral	N	0.488531536	None	None	N
G/T	0.2602	likely_benign	0.3081	benign	-0.77	Destabilizing	0.07	N	0.369	neutral	None	None	None	None	N
G/V	0.3645	ambiguous	0.4249	ambiguous	-0.528	Destabilizing	0.864	D	0.636	neutral	N	0.474204897	None	None	N
G/W	0.602	likely_pathogenic	0.6051	pathogenic	-1.197	Destabilizing	0.995	D	0.663	neutral	None	None	None	None	N
G/Y	0.5872	likely_pathogenic	0.6253	pathogenic	-0.917	Destabilizing	0.995	D	0.669	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.