TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20745	62458;62459;62460	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
N2AB	19104	57535;57536;57537	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
N2A	18177	54754;54755;54756	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
N2B	11680	35263;35264;35265	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
Novex-1	11805	35638;35639;35640	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
Novex-2	11872	35839;35840;35841	chr2:178589492;178589491;178589490	chr2:179454219;179454218;179454217
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: Fn3-38
• Domain position: 78
• Structural Position: 110
• Q(SASA): 0.0761
• 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	rs374085176	-2.337	0.37	N	0.34	0.116	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24008E-04	0	None	0	0	None	0	None	0	0	0
T/A	rs374085176	-2.337	0.37	N	0.34	0.116	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs374085176	-2.337	0.37	N	0.34	0.116	None	gnomAD-4.0.0	4.95877E-06	None	None	None	None	N	None	9.34554E-05	1.66845E-05	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	0.2519	likely_benign	0.2412	benign	-1.718	Destabilizing	0.37	N	0.34	neutral	N	0.295202799	None	None	N
T/C	0.6148	likely_pathogenic	0.5684	pathogenic	-1.726	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/D	0.9928	likely_pathogenic	0.9891	pathogenic	-2.691	Highly Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
T/E	0.9894	likely_pathogenic	0.9841	pathogenic	-2.493	Highly Destabilizing	0.995	D	0.784	deleterious	None	None	None	None	N
T/F	0.991	likely_pathogenic	0.9848	pathogenic	-1.243	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
T/G	0.7479	likely_pathogenic	0.7096	pathogenic	-1.977	Destabilizing	0.983	D	0.806	deleterious	None	None	None	None	N
T/H	0.9854	likely_pathogenic	0.976	pathogenic	-1.756	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
T/I	0.9572	likely_pathogenic	0.9345	pathogenic	-1.035	Destabilizing	0.997	D	0.806	deleterious	N	0.509915247	None	None	N
T/K	0.9901	likely_pathogenic	0.985	pathogenic	-1.174	Destabilizing	0.994	D	0.787	deleterious	N	0.509915247	None	None	N
T/L	0.8195	likely_pathogenic	0.7425	pathogenic	-1.035	Destabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
T/M	0.6727	likely_pathogenic	0.6096	pathogenic	-1.324	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/N	0.8868	likely_pathogenic	0.8373	pathogenic	-1.892	Destabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
T/P	0.9246	likely_pathogenic	0.8788	pathogenic	-1.244	Destabilizing	0.997	D	0.808	deleterious	N	0.47212765	None	None	N
T/Q	0.971	likely_pathogenic	0.9553	pathogenic	-1.617	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
T/R	0.981	likely_pathogenic	0.9695	pathogenic	-1.282	Destabilizing	0.997	D	0.803	deleterious	N	0.509915247	None	None	N
T/S	0.465	ambiguous	0.442	ambiguous	-1.942	Destabilizing	0.63	D	0.361	neutral	N	0.424680419	None	None	N
T/V	0.7076	likely_pathogenic	0.6463	pathogenic	-1.244	Destabilizing	0.983	D	0.631	neutral	None	None	None	None	N
T/W	0.9981	likely_pathogenic	0.9967	pathogenic	-1.549	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
T/Y	0.9909	likely_pathogenic	0.9845	pathogenic	-1.245	Destabilizing	0.999	D	0.868	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.