TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29074	87445;87446;87447	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
N2AB	27433	82522;82523;82524	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
N2A	26506	79741;79742;79743	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
N2B	20009	60250;60251;60252	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
Novex-1	20134	60625;60626;60627	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
Novex-2	20201	60826;60827;60828	chr2:178558134;178558133;178558132	chr2:179422861;179422860;179422859
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: Ig-145
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1934
• Predicted PPI site: I

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/A	rs761409208	-0.811	1.0	D	0.815	0.658	None	gnomAD-2.1.1	2.5E-05	None	None	None	None	I	None	2.89376E-04	0	None	0	0	None	0	None	0	0	0
P/A	rs761409208	-0.811	1.0	D	0.815	0.658	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	I	None	2.4122E-04	0	0	0	0	None	0	0	0	0	0
P/A	rs761409208	-0.811	1.0	D	0.815	0.658	None	gnomAD-4.0.0	1.05345E-05	None	None	None	None	I	None	2.2686E-04	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
P/A	0.6324	likely_pathogenic	0.6086	pathogenic	-1.356	Destabilizing	1.0	D	0.815	deleterious	D	0.52452291	None	None	I
P/C	0.9607	likely_pathogenic	0.9489	pathogenic	-0.991	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/D	0.9992	likely_pathogenic	0.9989	pathogenic	-0.91	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
P/E	0.9967	likely_pathogenic	0.9951	pathogenic	-0.938	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
P/F	0.9973	likely_pathogenic	0.9958	pathogenic	-1.182	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
P/G	0.9708	likely_pathogenic	0.9647	pathogenic	-1.642	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/H	0.9936	likely_pathogenic	0.9909	pathogenic	-1.205	Destabilizing	1.0	D	0.749	deleterious	D	0.537400153	None	None	I
P/I	0.9742	likely_pathogenic	0.9622	pathogenic	-0.691	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/K	0.9979	likely_pathogenic	0.9969	pathogenic	-1.054	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/L	0.8786	likely_pathogenic	0.8329	pathogenic	-0.691	Destabilizing	1.0	D	0.847	deleterious	D	0.532330362	None	None	I
P/M	0.9819	likely_pathogenic	0.9738	pathogenic	-0.542	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/N	0.9976	likely_pathogenic	0.9967	pathogenic	-0.806	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
P/Q	0.9882	likely_pathogenic	0.9829	pathogenic	-0.995	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
P/R	0.9918	likely_pathogenic	0.988	pathogenic	-0.558	Destabilizing	1.0	D	0.837	deleterious	D	0.536893174	None	None	I
P/S	0.9489	likely_pathogenic	0.9396	pathogenic	-1.344	Destabilizing	1.0	D	0.863	deleterious	D	0.536386195	None	None	I
P/T	0.9487	likely_pathogenic	0.9409	pathogenic	-1.258	Destabilizing	1.0	D	0.861	deleterious	D	0.536386195	None	None	I
P/V	0.924	likely_pathogenic	0.9007	pathogenic	-0.877	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
P/W	0.999	likely_pathogenic	0.9984	pathogenic	-1.312	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
P/Y	0.998	likely_pathogenic	0.9968	pathogenic	-1.021	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I

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.