TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7119	21580;21581;21582	chr2:178723904;178723903;178723902	chr2:179588631;179588630;179588629
N2AB	6802	20629;20630;20631	chr2:178723904;178723903;178723902	chr2:179588631;179588630;179588629
N2A	5875	17848;17849;17850	chr2:178723904;178723903;178723902	chr2:179588631;179588630;179588629
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-55
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2708
• 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
A/T	rs1254360704	-0.511	0.022	N	0.116	0.19	0.233150807113	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/T	rs1254360704	-0.511	0.022	N	0.116	0.19	0.233150807113	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86118E-06	0	0
A/V	None	None	0.051	N	0.273	0.237	0.410469974859	gnomAD-4.0.0	1.59253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02608E-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
A/C	0.553	ambiguous	0.5161	ambiguous	-1.022	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
A/D	0.2966	likely_benign	0.2698	benign	-0.961	Destabilizing	0.801	D	0.547	neutral	N	0.499600331	None	None	N
A/E	0.2274	likely_benign	0.2038	benign	-1.08	Destabilizing	0.842	D	0.473	neutral	None	None	None	None	N
A/F	0.3495	ambiguous	0.3184	benign	-1.276	Destabilizing	0.974	D	0.579	neutral	None	None	None	None	N
A/G	0.1742	likely_benign	0.1654	benign	-0.858	Destabilizing	0.454	N	0.377	neutral	N	0.512606914	None	None	N
A/H	0.4647	ambiguous	0.4233	ambiguous	-0.859	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
A/I	0.2878	likely_benign	0.256	benign	-0.615	Destabilizing	0.728	D	0.481	neutral	None	None	None	None	N
A/K	0.3875	ambiguous	0.3429	ambiguous	-0.869	Destabilizing	0.067	N	0.305	neutral	None	None	None	None	N
A/L	0.2255	likely_benign	0.2126	benign	-0.615	Destabilizing	0.525	D	0.458	neutral	None	None	None	None	N
A/M	0.2396	likely_benign	0.2209	benign	-0.488	Destabilizing	0.974	D	0.477	neutral	None	None	None	None	N
A/N	0.2587	likely_benign	0.2359	benign	-0.616	Destabilizing	0.842	D	0.545	neutral	None	None	None	None	N
A/P	0.8882	likely_pathogenic	0.8797	pathogenic	-0.622	Destabilizing	0.966	D	0.451	neutral	N	0.513306919	None	None	N
A/Q	0.3141	likely_benign	0.289	benign	-0.934	Destabilizing	0.949	D	0.457	neutral	None	None	None	None	N
A/R	0.3121	likely_benign	0.2812	benign	-0.404	Destabilizing	0.142	N	0.316	neutral	None	None	None	None	N
A/S	0.0876	likely_benign	0.085	benign	-0.886	Destabilizing	0.051	N	0.207	neutral	N	0.396395819	None	None	N
A/T	0.0744	likely_benign	0.0719	benign	-0.928	Destabilizing	0.022	N	0.116	neutral	N	0.40301236	None	None	N
A/V	0.1417	likely_benign	0.1291	benign	-0.622	Destabilizing	0.051	N	0.273	neutral	N	0.443669691	None	None	N
A/W	0.7152	likely_pathogenic	0.6674	pathogenic	-1.404	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
A/Y	0.4682	ambiguous	0.4212	ambiguous	-1.043	Destabilizing	0.991	D	0.575	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.