TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8430	25513;25514;25515	chr2:178717586;178717585;178717584	chr2:179582313;179582312;179582311
N2AB	8113	24562;24563;24564	chr2:178717586;178717585;178717584	chr2:179582313;179582312;179582311
N2A	7186	21781;21782;21783	chr2:178717586;178717585;178717584	chr2:179582313;179582312;179582311
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-69
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1089
• 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
Y/C	rs2077680471	None	1.0	D	0.866	0.866	0.812860075013	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	2.88184E-04	0	None	0	0	0	0	0
Y/C	rs2077680471	None	1.0	D	0.866	0.866	0.812860075013	gnomAD-4.0.0	2.02987E-06	None	None	None	None	N	None	0	0	None	1.15982E-04	0	None	0	0	1.20494E-06	0	0
Y/H	None	None	1.0	D	0.779	0.774	0.647653543843	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79929E-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
Y/A	0.9967	likely_pathogenic	0.9958	pathogenic	-2.611	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/C	0.97	likely_pathogenic	0.9587	pathogenic	-1.571	Destabilizing	1.0	D	0.866	deleterious	D	0.556685133	None	None	N
Y/D	0.9978	likely_pathogenic	0.9975	pathogenic	-3.336	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.568041439	None	None	N
Y/E	0.9986	likely_pathogenic	0.9985	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/F	0.2858	likely_benign	0.2592	benign	-1.029	Destabilizing	1.0	D	0.665	neutral	N	0.511091647	None	None	N
Y/G	0.9906	likely_pathogenic	0.9891	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/H	0.9882	likely_pathogenic	0.9843	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.779	deleterious	D	0.56753446	None	None	N
Y/I	0.9019	likely_pathogenic	0.8836	pathogenic	-1.133	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9987	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/L	0.8637	likely_pathogenic	0.8455	pathogenic	-1.133	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
Y/M	0.9754	likely_pathogenic	0.9699	pathogenic	-1.103	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/N	0.9886	likely_pathogenic	0.9868	pathogenic	-2.941	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.567787949	None	None	N
Y/P	0.9989	likely_pathogenic	0.9987	pathogenic	-1.644	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/Q	0.9988	likely_pathogenic	0.9985	pathogenic	-2.523	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/R	0.9961	likely_pathogenic	0.9951	pathogenic	-2.208	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/S	0.9942	likely_pathogenic	0.993	pathogenic	-3.176	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.567787949	None	None	N
Y/T	0.9967	likely_pathogenic	0.996	pathogenic	-2.789	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
Y/V	0.8661	likely_pathogenic	0.8472	pathogenic	-1.644	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/W	0.8652	likely_pathogenic	0.847	pathogenic	-0.4	Destabilizing	1.0	D	0.775	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.