TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1503	4732;4733;4734	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
N2AB	1503	4732;4733;4734	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
N2A	1503	4732;4733;4734	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
N2B	1457	4594;4595;4596	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
Novex-1	1457	4594;4595;4596	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
Novex-2	1457	4594;4595;4596	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283
Novex-3	1503	4732;4733;4734	chr2:178777558;178777557;178777556	chr2:179642285;179642284;179642283

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-6
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2839
• 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
H/R	None	None	1.0	N	0.653	0.714	0.468085328875	gnomAD-4.0.0	2.05249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79871E-06	1.15939E-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
H/A	0.9649	likely_pathogenic	0.9786	pathogenic	-1.514	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
H/C	0.5953	likely_pathogenic	0.685	pathogenic	-1.018	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
H/D	0.9537	likely_pathogenic	0.9725	pathogenic	-1.297	Destabilizing	1.0	D	0.695	prob.neutral	D	0.582194354	None	None	N
H/E	0.9356	likely_pathogenic	0.9623	pathogenic	-1.131	Destabilizing	0.999	D	0.467	neutral	None	None	None	None	N
H/F	0.9024	likely_pathogenic	0.9386	pathogenic	-0.021	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
H/G	0.955	likely_pathogenic	0.9726	pathogenic	-1.941	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
H/I	0.9711	likely_pathogenic	0.9834	pathogenic	-0.28	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
H/K	0.7712	likely_pathogenic	0.8362	pathogenic	-1.172	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
H/L	0.7961	likely_pathogenic	0.8423	pathogenic	-0.28	Destabilizing	1.0	D	0.781	deleterious	D	0.542898411	None	None	N
H/M	0.9719	likely_pathogenic	0.9817	pathogenic	-0.555	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
H/N	0.6671	likely_pathogenic	0.7654	pathogenic	-1.592	Destabilizing	0.999	D	0.477	neutral	D	0.601802526	None	None	N
H/P	0.9753	likely_pathogenic	0.9808	pathogenic	-0.676	Destabilizing	1.0	D	0.796	deleterious	N	0.507166245	None	None	N
H/Q	0.7563	likely_pathogenic	0.8414	pathogenic	-1.214	Destabilizing	1.0	D	0.702	prob.neutral	D	0.58783913	None	None	N
H/R	0.3763	ambiguous	0.4766	ambiguous	-1.513	Destabilizing	1.0	D	0.653	neutral	N	0.506562894	None	None	N
H/S	0.9013	likely_pathogenic	0.9399	pathogenic	-1.757	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
H/T	0.9507	likely_pathogenic	0.9721	pathogenic	-1.465	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
H/V	0.9449	likely_pathogenic	0.9663	pathogenic	-0.676	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
H/W	0.8209	likely_pathogenic	0.8677	pathogenic	0.422	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
H/Y	0.4412	ambiguous	0.5547	ambiguous	0.402	Stabilizing	0.999	D	0.515	neutral	N	0.502268666	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.