TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28545	85858;85859;85860	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
N2AB	26904	80935;80936;80937	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
N2A	25977	78154;78155;78156	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
N2B	19480	58663;58664;58665	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
Novex-1	19605	59038;59039;59040	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
Novex-2	19672	59239;59240;59241	chr2:178560499;178560498;178560497	chr2:179425226;179425225;179425224
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-95
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.3472
• 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
L/V	None	None	0.003	N	0.241	0.079	0.27855597813	gnomAD-4.0.0	6.84519E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99713E-07	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
L/A	0.1084	likely_benign	0.1095	benign	-1.166	Destabilizing	0.057	N	0.279	neutral	None	None	None	None	N
L/C	0.2756	likely_benign	0.2874	benign	-0.676	Destabilizing	0.96	D	0.281	neutral	None	None	None	None	N
L/D	0.4643	ambiguous	0.4612	ambiguous	-0.269	Destabilizing	0.507	D	0.63	neutral	None	None	None	None	N
L/E	0.1599	likely_benign	0.1573	benign	-0.326	Destabilizing	0.128	N	0.537	neutral	None	None	None	None	N
L/F	0.1218	likely_benign	0.1207	benign	-0.967	Destabilizing	0.507	D	0.352	neutral	None	None	None	None	N
L/G	0.3679	ambiguous	0.3711	ambiguous	-1.407	Destabilizing	0.507	D	0.578	neutral	None	None	None	None	N
L/H	0.1463	likely_benign	0.1396	benign	-0.628	Destabilizing	0.795	D	0.478	neutral	None	None	None	None	N
L/I	0.0712	likely_benign	0.069	benign	-0.62	Destabilizing	0.003	N	0.212	neutral	N	0.451456881	None	None	N
L/K	0.1256	likely_benign	0.1284	benign	-0.546	Destabilizing	0.128	N	0.475	neutral	None	None	None	None	N
L/M	0.0823	likely_benign	0.0817	benign	-0.432	Destabilizing	0.011	N	0.231	neutral	None	None	None	None	N
L/N	0.2472	likely_benign	0.2499	benign	-0.262	Destabilizing	0.507	D	0.663	prob.neutral	None	None	None	None	N
L/P	0.6816	likely_pathogenic	0.6742	pathogenic	-0.768	Destabilizing	0.612	D	0.663	prob.neutral	N	0.432180474	None	None	N
L/Q	0.0802	likely_benign	0.0744	benign	-0.499	Destabilizing	0.007	N	0.358	neutral	N	0.38946706	None	None	N
L/R	0.1064	likely_benign	0.1004	benign	0.024	Stabilizing	0.28	N	0.59	neutral	N	0.365032762	None	None	N
L/S	0.126	likely_benign	0.1285	benign	-0.872	Destabilizing	0.128	N	0.437	neutral	None	None	None	None	N
L/T	0.0915	likely_benign	0.0957	benign	-0.817	Destabilizing	0.227	N	0.397	neutral	None	None	None	None	N
L/V	0.0615	likely_benign	0.0617	benign	-0.768	Destabilizing	0.003	N	0.241	neutral	N	0.400644059	None	None	N
L/W	0.2311	likely_benign	0.2135	benign	-0.955	Destabilizing	0.96	D	0.558	neutral	None	None	None	None	N
L/Y	0.2755	likely_benign	0.2717	benign	-0.72	Destabilizing	0.676	D	0.431	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.