TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25473	76642;76643;76644	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
N2AB	23832	71719;71720;71721	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
N2A	22905	68938;68939;68940	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
N2B	16408	49447;49448;49449	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
Novex-1	16533	49822;49823;49824	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
Novex-2	16600	50023;50024;50025	chr2:178569715;178569714;178569713	chr2:179434442;179434441;179434440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-73
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.2734
• 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
E/G	None	None	0.988	N	0.68	0.482	0.458191732957	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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
E/A	0.2259	likely_benign	0.2196	benign	-0.805	Destabilizing	0.958	D	0.649	neutral	N	0.520441672	None	None	N
E/C	0.8936	likely_pathogenic	0.8978	pathogenic	-0.426	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.2765	likely_benign	0.2834	benign	-0.849	Destabilizing	0.067	N	0.223	neutral	N	0.489766209	None	None	N
E/F	0.8802	likely_pathogenic	0.8827	pathogenic	-0.421	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/G	0.2264	likely_benign	0.2137	benign	-1.103	Destabilizing	0.988	D	0.68	prob.neutral	N	0.496603064	None	None	N
E/H	0.7006	likely_pathogenic	0.6988	pathogenic	-0.53	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/I	0.5915	likely_pathogenic	0.5767	pathogenic	-0.012	Destabilizing	0.995	D	0.798	deleterious	None	None	None	None	N
E/K	0.3342	likely_benign	0.3371	benign	-0.47	Destabilizing	0.958	D	0.631	neutral	N	0.485460568	None	None	N
E/L	0.557	ambiguous	0.5431	ambiguous	-0.012	Destabilizing	0.995	D	0.773	deleterious	None	None	None	None	N
E/M	0.6451	likely_pathogenic	0.6408	pathogenic	0.291	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/N	0.5049	ambiguous	0.5064	ambiguous	-0.823	Destabilizing	0.982	D	0.761	deleterious	None	None	None	None	N
E/P	0.3673	ambiguous	0.3425	ambiguous	-0.255	Destabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
E/Q	0.2041	likely_benign	0.1935	benign	-0.745	Destabilizing	0.994	D	0.736	prob.delet.	N	0.482916127	None	None	N
E/R	0.4896	ambiguous	0.4818	ambiguous	-0.161	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	N
E/S	0.3439	ambiguous	0.3461	ambiguous	-1.074	Destabilizing	0.968	D	0.651	neutral	None	None	None	None	N
E/T	0.4199	ambiguous	0.4203	ambiguous	-0.839	Destabilizing	0.991	D	0.74	deleterious	None	None	None	None	N
E/V	0.3676	ambiguous	0.3501	ambiguous	-0.255	Destabilizing	0.994	D	0.75	deleterious	N	0.486474526	None	None	N
E/W	0.9474	likely_pathogenic	0.9484	pathogenic	-0.194	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/Y	0.8138	likely_pathogenic	0.8206	pathogenic	-0.19	Destabilizing	1.0	D	0.781	deleterious	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.