TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22739	68440;68441;68442	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
N2AB	21098	63517;63518;63519	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
N2A	20171	60736;60737;60738	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
N2B	13674	41245;41246;41247	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
Novex-1	13799	41620;41621;41622	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
Novex-2	13866	41821;41822;41823	chr2:178578815;178578814;178578813	chr2:179443542;179443541;179443540
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: Fn3-52
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.2758
• 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	rs1170829810	-0.118	0.938	N	0.678	0.282	0.247872288689	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
H/R	rs1170829810	-0.118	0.938	N	0.678	0.282	0.247872288689	gnomAD-4.0.0	1.6001E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44559E-05	0
H/Y	rs993803663	None	0.007	N	0.347	0.226	0.208816687407	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	6.32911E-03	0	0	4.79846E-04
H/Y	rs993803663	None	0.007	N	0.347	0.226	0.208816687407	gnomAD-4.0.0	8.07374E-06	None	None	None	None	I	None	1.33661E-05	0	None	0	0	None	0	1.49254E-03	0	0	4.81386E-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	0.9187	likely_pathogenic	0.9252	pathogenic	0.589	Stabilizing	0.74	D	0.576	neutral	None	None	None	None	I
H/C	0.6447	likely_pathogenic	0.6869	pathogenic	0.915	Stabilizing	0.996	D	0.838	deleterious	None	None	None	None	I
H/D	0.8605	likely_pathogenic	0.7756	pathogenic	0.014	Stabilizing	0.979	D	0.661	prob.neutral	N	0.443863613	None	None	I
H/E	0.9441	likely_pathogenic	0.942	pathogenic	0.029	Stabilizing	0.852	D	0.68	prob.neutral	None	None	None	None	I
H/F	0.5226	ambiguous	0.5972	pathogenic	1.171	Stabilizing	0.833	D	0.651	prob.neutral	None	None	None	None	I
H/G	0.9373	likely_pathogenic	0.9343	pathogenic	0.329	Stabilizing	0.852	D	0.516	neutral	None	None	None	None	I
H/I	0.8875	likely_pathogenic	0.9014	pathogenic	1.239	Stabilizing	0.909	D	0.77	deleterious	None	None	None	None	I
H/K	0.9463	likely_pathogenic	0.9562	pathogenic	0.546	Stabilizing	0.953	D	0.649	prob.neutral	None	None	None	None	I
H/L	0.3919	ambiguous	0.4477	ambiguous	1.239	Stabilizing	0.518	D	0.59	neutral	N	0.49544444	None	None	I
H/M	0.8721	likely_pathogenic	0.8847	pathogenic	0.917	Stabilizing	0.996	D	0.695	prob.delet.	None	None	None	None	I
H/N	0.4978	ambiguous	0.4242	ambiguous	0.515	Stabilizing	0.813	D	0.68	prob.neutral	N	0.442151459	None	None	I
H/P	0.5164	ambiguous	0.6056	pathogenic	1.048	Stabilizing	0.979	D	0.725	deleterious	N	0.518302657	None	None	I
H/Q	0.8926	likely_pathogenic	0.8971	pathogenic	0.591	Stabilizing	0.938	D	0.667	prob.neutral	N	0.507875019	None	None	I
H/R	0.8791	likely_pathogenic	0.9142	pathogenic	-0.054	Destabilizing	0.938	D	0.678	prob.neutral	N	0.507528302	None	None	I
H/S	0.8128	likely_pathogenic	0.7631	pathogenic	0.663	Stabilizing	0.852	D	0.653	prob.neutral	None	None	None	None	I
H/T	0.9297	likely_pathogenic	0.9236	pathogenic	0.774	Stabilizing	0.953	D	0.591	neutral	None	None	None	None	I
H/V	0.8916	likely_pathogenic	0.9118	pathogenic	1.048	Stabilizing	0.909	D	0.629	neutral	None	None	None	None	I
H/W	0.6776	likely_pathogenic	0.7303	pathogenic	1.088	Stabilizing	0.987	D	0.713	prob.delet.	None	None	None	None	I
H/Y	0.1737	likely_benign	0.2291	benign	1.389	Stabilizing	0.007	N	0.347	neutral	N	0.444132972	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.