TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5360	16303;16304;16305	chr2:178733098;178733097;178733096	chr2:179597825;179597824;179597823
N2AB	5043	15352;15353;15354	chr2:178733098;178733097;178733096	chr2:179597825;179597824;179597823
N2A	4116	12571;12572;12573	chr2:178733098;178733097;178733096	chr2:179597825;179597824;179597823
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-37
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4971
• 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
T/A	rs749081117	-0.621	0.998	N	0.374	0.256	0.139678290688	gnomAD-2.1.1	3.35E-05	None	None	None	None	N	None	0	2.63143E-04	None	0	0	None	0	None	0	0	0
T/A	rs749081117	-0.621	0.998	N	0.374	0.256	0.139678290688	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/A	rs749081117	-0.621	0.998	N	0.374	0.256	0.139678290688	gnomAD-4.0.0	5.00678E-06	None	None	None	None	N	None	0	1.36101E-04	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
T/A	0.1011	likely_benign	0.1106	benign	-0.729	Destabilizing	0.998	D	0.374	neutral	N	0.503308988	None	None	N
T/C	0.5253	ambiguous	0.5188	ambiguous	-0.417	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
T/D	0.6478	likely_pathogenic	0.6114	pathogenic	0.252	Stabilizing	0.504	D	0.285	neutral	None	None	None	None	N
T/E	0.4982	ambiguous	0.453	ambiguous	0.293	Stabilizing	0.994	D	0.56	neutral	None	None	None	None	N
T/F	0.3614	ambiguous	0.3423	ambiguous	-0.801	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/G	0.3237	likely_benign	0.3423	ambiguous	-0.996	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	N
T/H	0.3756	ambiguous	0.3662	ambiguous	-1.007	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/I	0.1559	likely_benign	0.1468	benign	-0.105	Destabilizing	1.0	D	0.681	prob.neutral	N	0.459920783	None	None	N
T/K	0.3245	likely_benign	0.3001	benign	-0.373	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
T/L	0.0944	likely_benign	0.093	benign	-0.105	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
T/M	0.1055	likely_benign	0.1061	benign	-0.143	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/N	0.2034	likely_benign	0.1976	benign	-0.465	Destabilizing	0.999	D	0.613	neutral	N	0.460758223	None	None	N
T/P	0.1773	likely_benign	0.193	benign	-0.281	Destabilizing	1.0	D	0.681	prob.neutral	N	0.490636858	None	None	N
T/Q	0.2906	likely_benign	0.2809	benign	-0.48	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/R	0.2468	likely_benign	0.2323	benign	-0.201	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
T/S	0.1392	likely_benign	0.1419	benign	-0.805	Destabilizing	0.996	D	0.365	neutral	N	0.44647427	None	None	N
T/V	0.1237	likely_benign	0.124	benign	-0.281	Destabilizing	1.0	D	0.505	neutral	None	None	None	None	N
T/W	0.6984	likely_pathogenic	0.6757	pathogenic	-0.811	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/Y	0.4124	ambiguous	0.3937	ambiguous	-0.521	Destabilizing	1.0	D	0.745	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.