TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20557	61894;61895;61896	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
N2AB	18916	56971;56972;56973	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
N2A	17989	54190;54191;54192	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
N2B	11492	34699;34700;34701	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
Novex-1	11617	35074;35075;35076	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
Novex-2	11684	35275;35276;35277	chr2:178590056;178590055;178590054	chr2:179454783;179454782;179454781
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-121
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.7807
• 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/D	rs1440800435	None	0.454	N	0.491	0.316	0.317084106153	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/D	rs1440800435	None	0.454	N	0.491	0.316	0.317084106153	gnomAD-4.0.0	6.57644E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47106E-05	0	0
H/R	rs1472565206	0.184	0.669	N	0.341	0.263	0.263612267334	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
H/R	rs1472565206	0.184	0.669	N	0.341	0.263	0.263612267334	gnomAD-4.0.0	1.36894E-06	None	None	None	None	I	None	2.99061E-05	0	None	0	0	None	0	0	8.99688E-07	0	0
H/Y	rs1440800435	None	0.961	N	0.419	0.289	0.342168650903	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs1440800435	None	0.961	N	0.419	0.289	0.342168650903	gnomAD-4.0.0	6.57644E-06	None	None	None	None	I	None	2.41348E-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
H/A	0.2098	likely_benign	0.241	benign	0.245	Stabilizing	0.688	D	0.577	neutral	None	None	None	None	I
H/C	0.1556	likely_benign	0.1869	benign	0.547	Stabilizing	0.998	D	0.567	neutral	None	None	None	None	I
H/D	0.2015	likely_benign	0.2757	benign	0.085	Stabilizing	0.454	N	0.491	neutral	N	0.415346939	None	None	I
H/E	0.1972	likely_benign	0.2484	benign	0.081	Stabilizing	0.01	N	0.158	neutral	None	None	None	None	I
H/F	0.1962	likely_benign	0.2059	benign	0.607	Stabilizing	0.991	D	0.488	neutral	None	None	None	None	I
H/G	0.3219	likely_benign	0.3873	ambiguous	0.016	Stabilizing	0.842	D	0.552	neutral	None	None	None	None	I
H/I	0.1763	likely_benign	0.1966	benign	0.802	Stabilizing	0.974	D	0.574	neutral	None	None	None	None	I
H/K	0.2147	likely_benign	0.2755	benign	0.211	Stabilizing	0.525	D	0.474	neutral	None	None	None	None	I
H/L	0.1006	likely_benign	0.1148	benign	0.802	Stabilizing	0.801	D	0.567	neutral	N	0.425467932	None	None	I
H/M	0.287	likely_benign	0.3014	benign	0.653	Stabilizing	0.991	D	0.547	neutral	None	None	None	None	I
H/N	0.0806	likely_benign	0.0956	benign	0.283	Stabilizing	0.801	D	0.353	neutral	N	0.424947857	None	None	I
H/P	0.4281	ambiguous	0.566	pathogenic	0.641	Stabilizing	0.891	D	0.539	neutral	N	0.444227051	None	None	I
H/Q	0.1209	likely_benign	0.1362	benign	0.304	Stabilizing	0.051	N	0.229	neutral	N	0.369246503	None	None	I
H/R	0.1298	likely_benign	0.1629	benign	-0.153	Destabilizing	0.669	D	0.341	neutral	N	0.376385906	None	None	I
H/S	0.1537	likely_benign	0.1701	benign	0.284	Stabilizing	0.688	D	0.469	neutral	None	None	None	None	I
H/T	0.1506	likely_benign	0.1655	benign	0.371	Stabilizing	0.842	D	0.546	neutral	None	None	None	None	I
H/V	0.1445	likely_benign	0.1607	benign	0.641	Stabilizing	0.915	D	0.585	neutral	None	None	None	None	I
H/W	0.3682	ambiguous	0.4124	ambiguous	0.54	Stabilizing	0.998	D	0.557	neutral	None	None	None	None	I
H/Y	0.0879	likely_benign	0.0999	benign	0.891	Stabilizing	0.961	D	0.419	neutral	N	0.433626056	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.