TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25897	77914;77915;77916	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
N2AB	24256	72991;72992;72993	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
N2A	23329	70210;70211;70212	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
N2B	16832	50719;50720;50721	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
Novex-1	16957	51094;51095;51096	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
Novex-2	17024	51295;51296;51297	chr2:178568443;178568442;178568441	chr2:179433170;179433169;179433168
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-76
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.2572
• 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
P/T	rs370103639	-1.247	1.0	N	0.817	0.41	0.444605663662	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
P/T	rs370103639	-1.247	1.0	N	0.817	0.41	0.444605663662	gnomAD-4.0.0	3.18475E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71938E-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
P/A	0.2763	likely_benign	0.3218	benign	-0.494	Destabilizing	1.0	D	0.767	deleterious	N	0.50224815	None	None	N
P/C	0.7626	likely_pathogenic	0.8028	pathogenic	-0.677	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
P/D	0.6881	likely_pathogenic	0.7222	pathogenic	-0.345	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/E	0.5603	ambiguous	0.6058	pathogenic	-0.456	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/F	0.8188	likely_pathogenic	0.8598	pathogenic	-0.683	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/G	0.6839	likely_pathogenic	0.7412	pathogenic	-0.62	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/H	0.5426	ambiguous	0.617	pathogenic	-0.12	Destabilizing	1.0	D	0.871	deleterious	D	0.528203218	None	None	N
P/I	0.5984	likely_pathogenic	0.6317	pathogenic	-0.309	Destabilizing	1.0	D	0.928	deleterious	None	None	None	None	N
P/K	0.6215	likely_pathogenic	0.676	pathogenic	-0.483	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/L	0.3385	likely_benign	0.3811	ambiguous	-0.309	Destabilizing	1.0	D	0.899	deleterious	N	0.500532494	None	None	N
P/M	0.584	likely_pathogenic	0.6233	pathogenic	-0.448	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/N	0.6456	likely_pathogenic	0.6981	pathogenic	-0.232	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/Q	0.4881	ambiguous	0.5516	ambiguous	-0.476	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/R	0.519	ambiguous	0.5837	pathogenic	0.053	Stabilizing	1.0	D	0.92	deleterious	N	0.507123222	None	None	N
P/S	0.459	ambiguous	0.5296	ambiguous	-0.583	Destabilizing	1.0	D	0.821	deleterious	N	0.502755129	None	None	N
P/T	0.3128	likely_benign	0.3653	ambiguous	-0.595	Destabilizing	1.0	D	0.817	deleterious	N	0.493209249	None	None	N
P/V	0.4618	ambiguous	0.4866	ambiguous	-0.337	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/W	0.9204	likely_pathogenic	0.9427	pathogenic	-0.744	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/Y	0.8018	likely_pathogenic	0.8504	pathogenic	-0.462	Destabilizing	1.0	D	0.912	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.