TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30228	90907;90908;90909	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
N2AB	28587	85984;85985;85986	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
N2A	27660	83203;83204;83205	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
N2B	21163	63712;63713;63714	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
Novex-1	21288	64087;64088;64089	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
Novex-2	21355	64288;64289;64290	chr2:178552218;178552217;178552216	chr2:179416945;179416944;179416943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-108
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1066
• 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/S	None	None	1.0	D	0.835	0.673	0.668985220733	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79921E-06	0	0
P/T	None	None	1.0	D	0.831	0.659	0.826159165136	gnomAD-4.0.0	6.84387E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99604E-07	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	0.833	likely_pathogenic	0.8015	pathogenic	-2.333	Highly Destabilizing	1.0	D	0.797	deleterious	D	0.540029818	None	None	N
P/C	0.9712	likely_pathogenic	0.9503	pathogenic	-1.998	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9991	pathogenic	-3.257	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/E	0.9968	likely_pathogenic	0.9963	pathogenic	-3.045	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/F	0.9988	likely_pathogenic	0.9983	pathogenic	-1.27	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/G	0.9917	likely_pathogenic	0.989	pathogenic	-2.841	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/H	0.9982	likely_pathogenic	0.9977	pathogenic	-2.52	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.581860642	None	None	N
P/I	0.8321	likely_pathogenic	0.7657	pathogenic	-0.902	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/K	0.9984	likely_pathogenic	0.9981	pathogenic	-1.976	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/L	0.8654	likely_pathogenic	0.8331	pathogenic	-0.902	Destabilizing	1.0	D	0.885	deleterious	D	0.580086215	None	None	N
P/M	0.9714	likely_pathogenic	0.9571	pathogenic	-1.122	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/N	0.998	likely_pathogenic	0.9971	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Q	0.9947	likely_pathogenic	0.9935	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/R	0.9957	likely_pathogenic	0.9955	pathogenic	-1.741	Destabilizing	1.0	D	0.893	deleterious	D	0.581353663	None	None	N
P/S	0.9882	likely_pathogenic	0.9825	pathogenic	-2.864	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.570250847	None	None	N
P/T	0.9402	likely_pathogenic	0.909	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.831	deleterious	D	0.580846684	None	None	N
P/V	0.6569	likely_pathogenic	0.5648	pathogenic	-1.355	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.809	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9992	pathogenic	-1.506	Destabilizing	1.0	D	0.889	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.