TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34413	103462;103463;103464	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
N2AB	32772	98539;98540;98541	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
N2A	31845	95758;95759;95760	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
N2B	25348	76267;76268;76269	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
Novex-1	25473	76642;76643;76644	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
Novex-2	25540	76843;76844;76845	chr2:178533378;178533377;178533376	chr2:179398105;179398104;179398103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-162
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.6345
• Predicted PPI site: I

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	rs778415445	-0.585	0.921	N	0.485	0.4	None	gnomAD-2.1.1	1.3205E-04	None	None	None	None	I	None	0	0	None	0	0	None	0	None	1.4881E-03	0	0
H/R	rs778415445	-0.585	0.921	N	0.485	0.4	None	gnomAD-3.1.2	1.31437E-04	None	None	None	None	I	None	0	0	0	0	0	None	1.88288E-03	0	0	0	0
H/R	rs778415445	-0.585	0.921	N	0.485	0.4	None	gnomAD-4.0.0	1.21732E-04	None	None	None	None	I	None	0	0	None	0	0	None	1.46591E-03	0	0	1.33998E-05	2.84398E-05

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	0.7282	likely_pathogenic	0.6299	pathogenic	-0.572	Destabilizing	0.969	D	0.57	neutral	None	None	None	None	I
H/C	0.4271	ambiguous	0.3638	ambiguous	0.026	Stabilizing	1.0	D	0.575	neutral	None	None	None	None	I
H/D	0.6693	likely_pathogenic	0.5543	ambiguous	-0.412	Destabilizing	0.959	D	0.508	neutral	N	0.447208641	None	None	I
H/E	0.592	likely_pathogenic	0.4851	ambiguous	-0.321	Destabilizing	0.864	D	0.478	neutral	None	None	None	None	I
H/F	0.6696	likely_pathogenic	0.6132	pathogenic	0.644	Stabilizing	0.999	D	0.519	neutral	None	None	None	None	I
H/G	0.7571	likely_pathogenic	0.6544	pathogenic	-0.916	Destabilizing	0.984	D	0.553	neutral	None	None	None	None	I
H/I	0.8191	likely_pathogenic	0.7539	pathogenic	0.366	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	I
H/K	0.4957	ambiguous	0.4215	ambiguous	-0.369	Destabilizing	0.293	N	0.325	neutral	None	None	None	None	I
H/L	0.4394	ambiguous	0.3744	ambiguous	0.366	Stabilizing	0.959	D	0.565	neutral	N	0.48276401	None	None	I
H/M	0.8361	likely_pathogenic	0.7766	pathogenic	0.109	Stabilizing	0.999	D	0.555	neutral	None	None	None	None	I
H/N	0.3379	likely_benign	0.2505	benign	-0.655	Destabilizing	0.979	D	0.495	neutral	N	0.444995055	None	None	I
H/P	0.5154	ambiguous	0.3873	ambiguous	0.075	Stabilizing	0.998	D	0.55	neutral	N	0.436954362	None	None	I
H/Q	0.3746	ambiguous	0.2886	benign	-0.449	Destabilizing	0.476	N	0.213	neutral	N	0.416693733	None	None	I
H/R	0.22	likely_benign	0.1769	benign	-0.777	Destabilizing	0.921	D	0.485	neutral	N	0.439589236	None	None	I
H/S	0.5362	ambiguous	0.4565	ambiguous	-0.68	Destabilizing	0.969	D	0.523	neutral	None	None	None	None	I
H/T	0.6855	likely_pathogenic	0.59	pathogenic	-0.476	Destabilizing	0.984	D	0.551	neutral	None	None	None	None	I
H/V	0.7394	likely_pathogenic	0.6728	pathogenic	0.075	Stabilizing	0.995	D	0.549	neutral	None	None	None	None	I
H/W	0.571	likely_pathogenic	0.5499	ambiguous	0.953	Stabilizing	1.0	D	0.58	neutral	None	None	None	None	I
H/Y	0.2413	likely_benign	0.1971	benign	1.001	Stabilizing	0.993	D	0.515	neutral	N	0.451806385	None	None	I

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.