TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20338	61237;61238;61239	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
N2AB	18697	56314;56315;56316	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
N2A	17770	53533;53534;53535	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
N2B	11273	34042;34043;34044	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
Novex-1	11398	34417;34418;34419	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
Novex-2	11465	34618;34619;34620	chr2:178590713;178590712;178590711	chr2:179455440;179455439;179455438
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: Fn3-35
• Domain position: 68
• Structural Position: 100
• Q(SASA): 0.2635
• 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/R	rs2050024015	None	1.0	N	0.833	0.626	0.800779853556	gnomAD-4.0.0	6.84607E-07	None	None	None	None	N	None	2.99079E-05	0	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
G/A	0.4685	ambiguous	0.5519	ambiguous	-0.35	Destabilizing	1.0	D	0.723	prob.delet.	N	0.489381951	None	None	N
G/C	0.5446	ambiguous	0.6275	pathogenic	-0.836	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/D	0.3905	ambiguous	0.4338	ambiguous	-0.962	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
G/E	0.5482	ambiguous	0.6042	pathogenic	-1.137	Destabilizing	1.0	D	0.842	deleterious	N	0.497117405	None	None	N
G/F	0.9002	likely_pathogenic	0.9297	pathogenic	-1.107	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/H	0.7266	likely_pathogenic	0.7938	pathogenic	-0.607	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/I	0.8743	likely_pathogenic	0.9195	pathogenic	-0.508	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/K	0.809	likely_pathogenic	0.8392	pathogenic	-0.973	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
G/L	0.8612	likely_pathogenic	0.8969	pathogenic	-0.508	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/M	0.8239	likely_pathogenic	0.8782	pathogenic	-0.463	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/N	0.3088	likely_benign	0.3681	ambiguous	-0.547	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
G/P	0.9891	likely_pathogenic	0.9932	pathogenic	-0.423	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/Q	0.6698	likely_pathogenic	0.7334	pathogenic	-0.899	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/R	0.7473	likely_pathogenic	0.782	pathogenic	-0.432	Destabilizing	1.0	D	0.833	deleterious	N	0.516640465	None	None	N
G/S	0.2277	likely_benign	0.2881	benign	-0.626	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/T	0.5017	ambiguous	0.6131	pathogenic	-0.749	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/V	0.7775	likely_pathogenic	0.8507	pathogenic	-0.423	Destabilizing	1.0	D	0.815	deleterious	D	0.551634434	None	None	N
G/W	0.7731	likely_pathogenic	0.8287	pathogenic	-1.246	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/Y	0.7594	likely_pathogenic	0.8171	pathogenic	-0.919	Destabilizing	1.0	D	0.793	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.