TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8347	25264;25265;25266	chr2:178717967;178717966;178717965	chr2:179582694;179582693;179582692
N2AB	8030	24313;24314;24315	chr2:178717967;178717966;178717965	chr2:179582694;179582693;179582692
N2A	7103	21532;21533;21534	chr2:178717967;178717966;178717965	chr2:179582694;179582693;179582692
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-68
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1278
• 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
S/P	rs1345180729	-0.261	0.917	D	0.801	0.427	0.404034981753	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.56E-05	None	0	None	0	0	0
S/P	rs1345180729	-0.261	0.917	D	0.801	0.427	0.404034981753	gnomAD-4.0.0	1.59401E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-05	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
S/A	0.1568	likely_benign	0.1758	benign	-0.913	Destabilizing	0.023	N	0.563	neutral	N	0.49124742	None	None	N
S/C	0.2058	likely_benign	0.2321	benign	-0.481	Destabilizing	0.005	N	0.55	neutral	N	0.466719909	None	None	N
S/D	0.9124	likely_pathogenic	0.9199	pathogenic	-0.07	Destabilizing	0.672	D	0.725	prob.delet.	None	None	None	None	N
S/E	0.9426	likely_pathogenic	0.9485	pathogenic	-0.049	Destabilizing	0.741	D	0.727	prob.delet.	None	None	None	None	N
S/F	0.7516	likely_pathogenic	0.8178	pathogenic	-1.043	Destabilizing	0.976	D	0.804	deleterious	N	0.504610413	None	None	N
S/G	0.2567	likely_benign	0.3163	benign	-1.188	Destabilizing	0.792	D	0.682	prob.neutral	None	None	None	None	N
S/H	0.8517	likely_pathogenic	0.882	pathogenic	-1.561	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
S/I	0.645	likely_pathogenic	0.7449	pathogenic	-0.279	Destabilizing	0.931	D	0.804	deleterious	None	None	None	None	N
S/K	0.9794	likely_pathogenic	0.9837	pathogenic	-0.592	Destabilizing	0.885	D	0.725	prob.delet.	None	None	None	None	N
S/L	0.3978	ambiguous	0.5135	ambiguous	-0.279	Destabilizing	0.793	D	0.737	prob.delet.	None	None	None	None	N
S/M	0.5763	likely_pathogenic	0.631	pathogenic	0.013	Stabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
S/N	0.6066	likely_pathogenic	0.657	pathogenic	-0.586	Destabilizing	0.194	N	0.729	prob.delet.	None	None	None	None	N
S/P	0.9683	likely_pathogenic	0.9824	pathogenic	-0.456	Destabilizing	0.917	D	0.801	deleterious	D	0.534324463	None	None	N
S/Q	0.9079	likely_pathogenic	0.9182	pathogenic	-0.683	Destabilizing	0.982	D	0.774	deleterious	None	None	None	None	N
S/R	0.9621	likely_pathogenic	0.9731	pathogenic	-0.539	Destabilizing	0.964	D	0.817	deleterious	None	None	None	None	N
S/T	0.11	likely_benign	0.104	benign	-0.641	Destabilizing	None	N	0.305	neutral	N	0.459388505	None	None	N
S/V	0.5028	ambiguous	0.5862	pathogenic	-0.456	Destabilizing	0.589	D	0.761	deleterious	None	None	None	None	N
S/W	0.8831	likely_pathogenic	0.9235	pathogenic	-0.99	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
S/Y	0.6943	likely_pathogenic	0.777	pathogenic	-0.73	Destabilizing	0.976	D	0.809	deleterious	D	0.522968158	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.