TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19471	58636;58637;58638	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
N2AB	17830	53713;53714;53715	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
N2A	16903	50932;50933;50934	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
N2B	10406	31441;31442;31443	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
Novex-1	10531	31816;31817;31818	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
Novex-2	10598	32017;32018;32019	chr2:178593982;178593981;178593980	chr2:179458709;179458708;179458707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-118
• Domain position: 81
• Structural Position: 171
• Q(SASA): 0.5
• 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
F/I	None	None	None	N	0.104	0.092	0.168933306366	gnomAD-4.0.0	6.8434E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99559E-07	0	0
F/L	rs867902753	None	None	N	0.118	0.092	0.556540827966	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/L	rs867902753	None	None	N	0.118	0.092	0.556540827966	gnomAD-4.0.0	6.57592E-06	None	None	None	None	N	None	2.41418E-05	0	None	0	0	None	0	0	0	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
F/A	0.2971	likely_benign	0.3357	benign	-1.135	Destabilizing	None	N	0.211	neutral	None	None	None	None	N
F/C	0.2014	likely_benign	0.2034	benign	-0.32	Destabilizing	0.196	N	0.551	neutral	D	0.523687912	None	None	N
F/D	0.4893	ambiguous	0.4882	ambiguous	0.609	Stabilizing	0.044	N	0.545	neutral	None	None	None	None	N
F/E	0.5281	ambiguous	0.5231	ambiguous	0.606	Stabilizing	0.009	N	0.501	neutral	None	None	None	None	N
F/G	0.5729	likely_pathogenic	0.5949	pathogenic	-1.364	Destabilizing	0.009	N	0.459	neutral	None	None	None	None	N
F/H	0.3442	ambiguous	0.3611	ambiguous	0.088	Stabilizing	0.138	N	0.505	neutral	None	None	None	None	N
F/I	0.0797	likely_benign	0.0908	benign	-0.527	Destabilizing	None	N	0.104	neutral	N	0.414712221	None	None	N
F/K	0.6207	likely_pathogenic	0.6171	pathogenic	-0.206	Destabilizing	0.009	N	0.506	neutral	None	None	None	None	N
F/L	0.5755	likely_pathogenic	0.587	pathogenic	-0.527	Destabilizing	None	N	0.118	neutral	N	0.456366842	None	None	N
F/M	0.2533	likely_benign	0.284	benign	-0.408	Destabilizing	0.138	N	0.436	neutral	None	None	None	None	N
F/N	0.2672	likely_benign	0.3158	benign	-0.11	Destabilizing	0.022	N	0.593	neutral	None	None	None	None	N
F/P	0.897	likely_pathogenic	0.9053	pathogenic	-0.712	Destabilizing	0.085	N	0.597	neutral	None	None	None	None	N
F/Q	0.5192	ambiguous	0.5348	ambiguous	-0.17	Destabilizing	0.044	N	0.647	neutral	None	None	None	None	N
F/R	0.5477	ambiguous	0.5389	ambiguous	0.275	Stabilizing	0.044	N	0.599	neutral	None	None	None	None	N
F/S	0.1768	likely_benign	0.1961	benign	-0.825	Destabilizing	None	N	0.228	neutral	N	0.396123673	None	None	N
F/T	0.1888	likely_benign	0.2064	benign	-0.734	Destabilizing	None	N	0.23	neutral	None	None	None	None	N
F/V	0.0973	likely_benign	0.1048	benign	-0.712	Destabilizing	None	N	0.137	neutral	N	0.474779245	None	None	N
F/W	0.3798	ambiguous	0.3466	ambiguous	-0.227	Destabilizing	0.245	N	0.455	neutral	None	None	None	None	N
F/Y	0.1155	likely_benign	0.1208	benign	-0.263	Destabilizing	None	N	0.13	neutral	N	0.471258937	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.