TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25539	76840;76841;76842	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
N2AB	23898	71917;71918;71919	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
N2A	22971	69136;69137;69138	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
N2B	16474	49645;49646;49647	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
Novex-1	16599	50020;50021;50022	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
Novex-2	16666	50221;50222;50223	chr2:178569517;178569516;178569515	chr2:179434244;179434243;179434242
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-135
• Domain position: 26
• Structural Position: 43
• Q(SASA): 0.6897
• 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
T/I	rs746337217	0.068	0.627	N	0.375	0.437	0.401185642668	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	8.91E-06	0
T/I	rs746337217	0.068	0.627	N	0.375	0.437	0.401185642668	gnomAD-4.0.0	2.73857E-06	None	None	None	None	I	None	0	2.23994E-05	None	0	0	None	0	0	1.79969E-06	0	1.65788E-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
T/A	0.057	likely_benign	0.0572	benign	-0.584	Destabilizing	None	N	0.145	neutral	N	0.473664524	None	None	I
T/C	0.3131	likely_benign	0.3407	ambiguous	-0.367	Destabilizing	0.944	D	0.381	neutral	None	None	None	None	I
T/D	0.32	likely_benign	0.3534	ambiguous	0.101	Stabilizing	0.563	D	0.389	neutral	None	None	None	None	I
T/E	0.2357	likely_benign	0.2584	benign	0.043	Stabilizing	0.388	N	0.347	neutral	None	None	None	None	I
T/F	0.1594	likely_benign	0.1794	benign	-0.901	Destabilizing	0.818	D	0.466	neutral	None	None	None	None	I
T/G	0.2561	likely_benign	0.2813	benign	-0.757	Destabilizing	0.116	N	0.395	neutral	None	None	None	None	I
T/H	0.243	likely_benign	0.2593	benign	-1.098	Destabilizing	0.981	D	0.46	neutral	None	None	None	None	I
T/I	0.0753	likely_benign	0.0846	benign	-0.235	Destabilizing	0.627	D	0.375	neutral	N	0.521919831	None	None	I
T/K	0.1859	likely_benign	0.2065	benign	-0.585	Destabilizing	0.324	N	0.359	neutral	N	0.496944028	None	None	I
T/L	0.0632	likely_benign	0.0678	benign	-0.235	Destabilizing	0.241	N	0.326	neutral	None	None	None	None	I
T/M	0.0709	likely_benign	0.0715	benign	0.018	Stabilizing	0.818	D	0.383	neutral	None	None	None	None	I
T/N	0.116	likely_benign	0.1234	benign	-0.339	Destabilizing	0.818	D	0.323	neutral	None	None	None	None	I
T/P	0.0824	likely_benign	0.0804	benign	-0.322	Destabilizing	0.001	N	0.205	neutral	N	0.49781082	None	None	I
T/Q	0.1903	likely_benign	0.2008	benign	-0.579	Destabilizing	0.818	D	0.389	neutral	None	None	None	None	I
T/R	0.1793	likely_benign	0.196	benign	-0.329	Destabilizing	0.627	D	0.377	neutral	N	0.513414991	None	None	I
T/S	0.1015	likely_benign	0.1058	benign	-0.597	Destabilizing	0.09	N	0.294	neutral	N	0.500773767	None	None	I
T/V	0.0643	likely_benign	0.0699	benign	-0.322	Destabilizing	0.116	N	0.25	neutral	None	None	None	None	I
T/W	0.5733	likely_pathogenic	0.6046	pathogenic	-0.842	Destabilizing	0.981	D	0.527	neutral	None	None	None	None	I
T/Y	0.2332	likely_benign	0.2588	benign	-0.604	Destabilizing	0.932	D	0.469	neutral	None	None	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.