TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23988	72187;72188;72189	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
N2AB	22347	67264;67265;67266	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
N2A	21420	64483;64484;64485	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
N2B	14923	44992;44993;44994	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
Novex-1	15048	45367;45368;45369	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
Novex-2	15115	45568;45569;45570	chr2:178574170;178574169;178574168	chr2:179438897;179438896;179438895
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: Fn3-62
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.5643
• 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/D	rs1320505610	None	1.0	N	0.743	0.525	0.177238962908	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/D	rs1320505610	None	1.0	N	0.743	0.525	0.177238962908	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	2.41383E-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	0.3048	likely_benign	0.3339	benign	-0.187	Destabilizing	1.0	D	0.679	prob.neutral	N	0.476944056	None	None	N
G/C	0.5036	ambiguous	0.529	ambiguous	-0.804	Destabilizing	1.0	D	0.733	prob.delet.	D	0.522560315	None	None	N
G/D	0.6396	likely_pathogenic	0.6573	pathogenic	-0.324	Destabilizing	1.0	D	0.743	deleterious	N	0.478298687	None	None	N
G/E	0.6867	likely_pathogenic	0.7165	pathogenic	-0.48	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
G/F	0.8737	likely_pathogenic	0.9	pathogenic	-0.898	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/H	0.7897	likely_pathogenic	0.8096	pathogenic	-0.418	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/I	0.7614	likely_pathogenic	0.802	pathogenic	-0.317	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/K	0.8993	likely_pathogenic	0.9203	pathogenic	-0.67	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
G/L	0.7894	likely_pathogenic	0.8291	pathogenic	-0.317	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/M	0.8091	likely_pathogenic	0.8367	pathogenic	-0.446	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/N	0.5318	ambiguous	0.5385	ambiguous	-0.31	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/P	0.9731	likely_pathogenic	0.9743	pathogenic	-0.241	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
G/Q	0.7395	likely_pathogenic	0.7703	pathogenic	-0.562	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/R	0.781	likely_pathogenic	0.8303	pathogenic	-0.276	Destabilizing	1.0	D	0.767	deleterious	N	0.474791236	None	None	N
G/S	0.1733	likely_benign	0.1927	benign	-0.483	Destabilizing	1.0	D	0.75	deleterious	N	0.477727297	None	None	N
G/T	0.4626	ambiguous	0.4847	ambiguous	-0.561	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/V	0.6222	likely_pathogenic	0.6716	pathogenic	-0.241	Destabilizing	1.0	D	0.751	deleterious	D	0.533916621	None	None	N
G/W	0.8208	likely_pathogenic	0.8492	pathogenic	-1.066	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
G/Y	0.8182	likely_pathogenic	0.8409	pathogenic	-0.701	Destabilizing	1.0	D	0.743	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.