TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26230	78913;78914;78915	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
N2AB	24589	73990;73991;73992	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
N2A	23662	71209;71210;71211	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
N2B	17165	51718;51719;51720	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
Novex-1	17290	52093;52094;52095	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
Novex-2	17357	52294;52295;52296	chr2:178567444;178567443;178567442	chr2:179432171;179432170;179432169
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: Ig-137
• Domain position: 38
• Structural Position: 51
• Q(SASA): 0.3644
• 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	N	0.754	0.364	0.493021045079	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1993	likely_benign	0.1773	benign	-0.398	Destabilizing	1.0	D	0.575	neutral	N	0.482723071	None	None	N
G/C	0.291	likely_benign	0.2362	benign	-0.831	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/D	0.2059	likely_benign	0.1842	benign	-0.581	Destabilizing	0.921	D	0.551	neutral	None	None	None	None	N
G/E	0.282	likely_benign	0.2535	benign	-0.687	Destabilizing	1.0	D	0.739	prob.delet.	N	0.448013065	None	None	N
G/F	0.784	likely_pathogenic	0.7249	pathogenic	-0.83	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
G/H	0.5449	ambiguous	0.4798	ambiguous	-0.855	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
G/I	0.6579	likely_pathogenic	0.5679	pathogenic	-0.24	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
G/K	0.585	likely_pathogenic	0.5421	ambiguous	-1.059	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
G/L	0.6161	likely_pathogenic	0.544	ambiguous	-0.24	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/M	0.6386	likely_pathogenic	0.5671	pathogenic	-0.319	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
G/N	0.226	likely_benign	0.1949	benign	-0.69	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
G/P	0.9679	likely_pathogenic	0.9522	pathogenic	-0.253	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
G/Q	0.4226	ambiguous	0.3812	ambiguous	-0.893	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/R	0.4835	ambiguous	0.4419	ambiguous	-0.702	Destabilizing	1.0	D	0.733	prob.delet.	N	0.454263763	None	None	N
G/S	0.1505	likely_benign	0.1341	benign	-0.917	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
G/T	0.4327	ambiguous	0.3696	ambiguous	-0.941	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/V	0.5007	ambiguous	0.4162	ambiguous	-0.253	Destabilizing	1.0	D	0.754	deleterious	N	0.506312007	None	None	N
G/W	0.6115	likely_pathogenic	0.5386	ambiguous	-1.113	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
G/Y	0.57	likely_pathogenic	0.4915	ambiguous	-0.719	Destabilizing	1.0	D	0.689	prob.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.