TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
N2AB	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
N2A	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
N2B	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
Novex-1	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
Novex-2	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240
Novex-3	155	688;689;690	chr2:178800515;178800514;178800513	chr2:179665242;179665241;179665240

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-2
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.6344
• 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
E/Q	rs1429805491	0.676	0.623	N	0.35	0.205	0.266385636622	gnomAD-2.1.1	3.98E-06	None	None	None	-1.009(TCAP)	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs1429805491	0.676	0.623	N	0.35	0.205	0.266385636622	gnomAD-4.0.0	1.59045E-06	None	None	None	-1.009(TCAP)	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
E/A	0.3041	likely_benign	0.3877	ambiguous	-0.22	Destabilizing	0.38	N	0.393	neutral	N	0.504131086	None	-0.276(TCAP)	N
E/C	0.9867	likely_pathogenic	0.9911	pathogenic	0.082	Stabilizing	0.985	D	0.411	neutral	None	None	None	-0.242(TCAP)	N
E/D	0.2291	likely_benign	0.246	benign	-0.175	Destabilizing	None	N	0.157	neutral	N	0.463312521	None	-0.152(TCAP)	N
E/F	0.9524	likely_pathogenic	0.9671	pathogenic	-0.2	Destabilizing	0.97	D	0.363	neutral	None	None	None	-0.153(TCAP)	N
E/G	0.4418	ambiguous	0.5554	ambiguous	-0.361	Destabilizing	0.672	D	0.388	neutral	N	0.516305462	None	-0.441(TCAP)	N
E/H	0.8091	likely_pathogenic	0.8599	pathogenic	0.131	Stabilizing	0.885	D	0.305	neutral	None	None	None	0.497(TCAP)	N
E/I	0.7104	likely_pathogenic	0.7788	pathogenic	0.101	Stabilizing	0.834	D	0.372	neutral	None	None	None	0.213(TCAP)	N
E/K	0.3933	ambiguous	0.478	ambiguous	0.602	Stabilizing	0.532	D	0.398	neutral	N	0.499629298	None	-0.019(TCAP)	N
E/L	0.8058	likely_pathogenic	0.8571	pathogenic	0.101	Stabilizing	0.834	D	0.368	neutral	None	None	None	0.213(TCAP)	N
E/M	0.8048	likely_pathogenic	0.8453	pathogenic	0.147	Stabilizing	0.912	D	0.379	neutral	None	None	None	0.902(TCAP)	N
E/N	0.5173	ambiguous	0.5868	pathogenic	0.269	Stabilizing	0.004	N	0.239	neutral	None	None	None	-1.652(TCAP)	N
E/P	0.955	likely_pathogenic	0.973	pathogenic	0.012	Stabilizing	0.427	N	0.335	neutral	None	None	None	0.055(TCAP)	N
E/Q	0.2811	likely_benign	0.3286	benign	0.3	Stabilizing	0.623	D	0.35	neutral	N	0.513133156	None	-1.009(TCAP)	N
E/R	0.5758	likely_pathogenic	0.6668	pathogenic	0.691	Stabilizing	0.915	D	0.304	neutral	None	None	None	-0.127(TCAP)	N
E/S	0.3966	ambiguous	0.4744	ambiguous	0.158	Stabilizing	0.449	N	0.373	neutral	None	None	None	-1.36(TCAP)	N
E/T	0.4252	ambiguous	0.5153	ambiguous	0.286	Stabilizing	0.529	D	0.404	neutral	None	None	None	-1.176(TCAP)	N
E/V	0.4435	ambiguous	0.5244	ambiguous	0.012	Stabilizing	0.729	D	0.362	neutral	D	0.553055496	None	0.055(TCAP)	N
E/W	0.9841	likely_pathogenic	0.9896	pathogenic	-0.097	Destabilizing	0.997	D	0.515	neutral	None	None	None	-0.339(TCAP)	N
E/Y	0.9155	likely_pathogenic	0.939	pathogenic	0.036	Stabilizing	0.989	D	0.367	neutral	None	None	None	-0.229(TCAP)	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.