TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10128	30607;30608;30609	chr2:178702505;178702504;178702503	chr2:179567232;179567231;179567230
N2AB	9811	29656;29657;29658	chr2:178702505;178702504;178702503	chr2:179567232;179567231;179567230
N2A	8884	26875;26876;26877	chr2:178702505;178702504;178702503	chr2:179567232;179567231;179567230
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-86
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.7247
• 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
D/Y	None	None	0.997	None	0.585	0.363	0.792777554351	gnomAD-4.0.0	1.36826E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79878E-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
D/A	0.7453	likely_pathogenic	0.6134	pathogenic	-0.132	Destabilizing	0.939	D	0.455	neutral	None	None	None	None	N
D/C	0.9807	likely_pathogenic	0.9691	pathogenic	-0.009	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	N
D/E	0.5729	likely_pathogenic	0.4151	ambiguous	-0.244	Destabilizing	0.02	N	0.191	neutral	None	None	None	None	N
D/F	0.9627	likely_pathogenic	0.93	pathogenic	-0.113	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
D/G	0.8319	likely_pathogenic	0.7797	pathogenic	-0.304	Destabilizing	0.939	D	0.453	neutral	None	None	None	None	N
D/H	0.8554	likely_pathogenic	0.773	pathogenic	0.225	Stabilizing	0.998	D	0.464	neutral	None	None	None	None	N
D/I	0.9079	likely_pathogenic	0.8036	pathogenic	0.264	Stabilizing	0.993	D	0.603	neutral	None	None	None	None	N
D/K	0.8989	likely_pathogenic	0.8234	pathogenic	0.357	Stabilizing	0.91	D	0.44	neutral	None	None	None	None	N
D/L	0.9093	likely_pathogenic	0.8441	pathogenic	0.264	Stabilizing	0.986	D	0.613	neutral	None	None	None	None	N
D/M	0.9689	likely_pathogenic	0.9422	pathogenic	0.247	Stabilizing	0.999	D	0.592	neutral	None	None	None	None	N
D/N	0.4139	ambiguous	0.3209	benign	0.107	Stabilizing	0.939	D	0.421	neutral	None	None	None	None	N
D/P	0.9954	likely_pathogenic	0.9946	pathogenic	0.153	Stabilizing	0.993	D	0.471	neutral	None	None	None	None	N
D/Q	0.867	likely_pathogenic	0.7757	pathogenic	0.136	Stabilizing	0.973	D	0.384	neutral	None	None	None	None	N
D/R	0.8902	likely_pathogenic	0.817	pathogenic	0.571	Stabilizing	0.986	D	0.566	neutral	None	None	None	None	N
D/S	0.5609	ambiguous	0.435	ambiguous	-0.007	Destabilizing	0.953	D	0.39	neutral	None	None	None	None	N
D/T	0.7952	likely_pathogenic	0.6972	pathogenic	0.128	Stabilizing	0.986	D	0.419	neutral	None	None	None	None	N
D/V	0.7784	likely_pathogenic	0.6057	pathogenic	0.153	Stabilizing	0.991	D	0.608	neutral	None	None	None	None	N
D/W	0.9898	likely_pathogenic	0.9869	pathogenic	-0.018	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
D/Y	0.7981	likely_pathogenic	0.6952	pathogenic	0.121	Stabilizing	0.997	D	0.585	neutral	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.