TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26237	78934;78935;78936	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
N2AB	24596	74011;74012;74013	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
N2A	23669	71230;71231;71232	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
N2B	17172	51739;51740;51741	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
Novex-1	17297	52114;52115;52116	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
Novex-2	17364	52315;52316;52317	chr2:178567423;178567422;178567421	chr2:179432150;179432149;179432148
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-137
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.3234
• 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/F	rs1706305589	None	0.901	N	0.537	0.374	0.515430650102	gnomAD-4.0.0	1.60647E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87747E-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
S/A	0.1311	likely_benign	0.1189	benign	-0.119	Destabilizing	0.349	N	0.452	neutral	N	0.491555985	None	None	N
S/C	0.2105	likely_benign	0.172	benign	-0.237	Destabilizing	0.995	D	0.406	neutral	N	0.502832991	None	None	N
S/D	0.4874	ambiguous	0.4253	ambiguous	-0.08	Destabilizing	0.775	D	0.436	neutral	None	None	None	None	N
S/E	0.73	likely_pathogenic	0.6891	pathogenic	-0.192	Destabilizing	0.775	D	0.428	neutral	None	None	None	None	N
S/F	0.4814	ambiguous	0.4036	ambiguous	-0.829	Destabilizing	0.901	D	0.537	neutral	N	0.484475247	None	None	N
S/G	0.0992	likely_benign	0.0849	benign	-0.176	Destabilizing	0.775	D	0.427	neutral	None	None	None	None	N
S/H	0.5601	ambiguous	0.4884	ambiguous	-0.588	Destabilizing	0.996	D	0.401	neutral	None	None	None	None	N
S/I	0.3783	ambiguous	0.3186	benign	-0.102	Destabilizing	0.633	D	0.512	neutral	None	None	None	None	N
S/K	0.7782	likely_pathogenic	0.7138	pathogenic	-0.412	Destabilizing	0.775	D	0.425	neutral	None	None	None	None	N
S/L	0.175	likely_benign	0.146	benign	-0.102	Destabilizing	0.011	N	0.301	neutral	None	None	None	None	N
S/M	0.2414	likely_benign	0.2056	benign	0.003	Stabilizing	0.923	D	0.391	neutral	None	None	None	None	N
S/N	0.1577	likely_benign	0.1309	benign	-0.086	Destabilizing	0.775	D	0.478	neutral	None	None	None	None	N
S/P	0.722	likely_pathogenic	0.6513	pathogenic	-0.082	Destabilizing	0.949	D	0.401	neutral	N	0.462483425	None	None	N
S/Q	0.7187	likely_pathogenic	0.6606	pathogenic	-0.349	Destabilizing	0.961	D	0.402	neutral	None	None	None	None	N
S/R	0.7832	likely_pathogenic	0.7211	pathogenic	-0.154	Destabilizing	0.923	D	0.397	neutral	None	None	None	None	N
S/T	0.0651	likely_benign	0.0607	benign	-0.187	Destabilizing	0.003	N	0.209	neutral	N	0.432854399	None	None	N
S/V	0.3291	likely_benign	0.2775	benign	-0.082	Destabilizing	0.633	D	0.47	neutral	None	None	None	None	N
S/W	0.6358	likely_pathogenic	0.5672	pathogenic	-0.912	Destabilizing	0.996	D	0.661	neutral	None	None	None	None	N
S/Y	0.3956	ambiguous	0.3383	benign	-0.601	Destabilizing	0.949	D	0.543	neutral	N	0.484475247	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.