TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15639	47140;47141;47142	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
N2AB	13998	42217;42218;42219	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
N2A	13071	39436;39437;39438	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
N2B	6574	19945;19946;19947	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
Novex-1	6699	20320;20321;20322	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
Novex-2	6766	20521;20522;20523	chr2:178618635;178618634;178618633	chr2:179483362;179483361;179483360
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-108
• Domain position: 72
• Structural Position: 158
• Q(SASA): 0.0724
• 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
L/F	rs1226774486	None	0.994	N	0.759	0.356	0.654265926928	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1226774486	None	0.994	N	0.759	0.356	0.654265926928	gnomAD-4.0.0	3.85041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19193E-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
L/A	0.7993	likely_pathogenic	0.8233	pathogenic	-3.017	Highly Destabilizing	0.97	D	0.719	prob.delet.	None	None	None	None	N
L/C	0.7759	likely_pathogenic	0.8043	pathogenic	-2.306	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9987	pathogenic	-3.629	Highly Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
L/E	0.9917	likely_pathogenic	0.9908	pathogenic	-3.402	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
L/F	0.3862	ambiguous	0.4619	ambiguous	-1.735	Destabilizing	0.994	D	0.759	deleterious	N	0.507032058	None	None	N
L/G	0.966	likely_pathogenic	0.9692	pathogenic	-3.544	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
L/H	0.9727	likely_pathogenic	0.974	pathogenic	-2.903	Highly Destabilizing	1.0	D	0.831	deleterious	N	0.508103218	None	None	N
L/I	0.1148	likely_benign	0.1227	benign	-1.466	Destabilizing	0.122	N	0.283	neutral	N	0.499289699	None	None	N
L/K	0.9865	likely_pathogenic	0.9834	pathogenic	-2.459	Highly Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
L/M	0.2602	likely_benign	0.3036	benign	-1.464	Destabilizing	0.996	D	0.751	deleterious	None	None	None	None	N
L/N	0.991	likely_pathogenic	0.9884	pathogenic	-2.839	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/P	0.9928	likely_pathogenic	0.9934	pathogenic	-1.97	Destabilizing	0.998	D	0.841	deleterious	N	0.507897754	None	None	N
L/Q	0.958	likely_pathogenic	0.9552	pathogenic	-2.707	Highly Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
L/R	0.9673	likely_pathogenic	0.9657	pathogenic	-2.048	Highly Destabilizing	0.998	D	0.813	deleterious	N	0.507897754	None	None	N
L/S	0.9643	likely_pathogenic	0.9682	pathogenic	-3.468	Highly Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
L/T	0.8894	likely_pathogenic	0.8914	pathogenic	-3.114	Highly Destabilizing	0.97	D	0.764	deleterious	None	None	None	None	N
L/V	0.1482	likely_benign	0.1762	benign	-1.97	Destabilizing	0.248	N	0.336	neutral	N	0.493653518	None	None	N
L/W	0.9109	likely_pathogenic	0.9322	pathogenic	-2.17	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
L/Y	0.9147	likely_pathogenic	0.9296	pathogenic	-1.984	Destabilizing	0.999	D	0.804	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.