TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14122	42589;42590;42591	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
N2AB	12481	37666;37667;37668	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
N2A	11554	34885;34886;34887	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
N2B	5057	15394;15395;15396	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
Novex-1	5182	15769;15770;15771	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
Novex-2	5249	15970;15971;15972	chr2:178634417;178634416;178634415	chr2:179499144;179499143;179499142
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-91
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.1098
• 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	rs756627487	-1.239	1.0	D	0.877	0.707	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
Y/C	rs756627487	-1.239	1.0	D	0.877	0.707	None	gnomAD-4.0.0	6.16064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19766E-06	1.1598E-05	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	0.9968	likely_pathogenic	0.9961	pathogenic	-1.845	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
Y/C	0.9422	likely_pathogenic	0.9265	pathogenic	-1.356	Destabilizing	1.0	D	0.877	deleterious	D	0.789211171	None	None	N
Y/D	0.9988	likely_pathogenic	0.9977	pathogenic	-2.537	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.789211171	None	None	N
Y/E	0.9992	likely_pathogenic	0.9988	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/F	0.251	likely_benign	0.2537	benign	-0.564	Destabilizing	0.434	N	0.414	neutral	D	0.643718253	None	None	N
Y/G	0.995	likely_pathogenic	0.9942	pathogenic	-2.294	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/H	0.9868	likely_pathogenic	0.9795	pathogenic	-1.949	Destabilizing	1.0	D	0.733	prob.delet.	D	0.789832162	None	None	N
Y/I	0.8863	likely_pathogenic	0.9238	pathogenic	-0.37	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
Y/K	0.999	likely_pathogenic	0.9984	pathogenic	-1.634	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/L	0.8245	likely_pathogenic	0.8716	pathogenic	-0.37	Destabilizing	0.994	D	0.757	deleterious	None	None	None	None	N
Y/M	0.9753	likely_pathogenic	0.9777	pathogenic	-0.546	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/N	0.9929	likely_pathogenic	0.989	pathogenic	-2.554	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.789211171	None	None	N
Y/P	0.9986	likely_pathogenic	0.9983	pathogenic	-0.876	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/Q	0.9991	likely_pathogenic	0.9985	pathogenic	-2.032	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/R	0.9955	likely_pathogenic	0.9937	pathogenic	-2.104	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/S	0.9945	likely_pathogenic	0.9918	pathogenic	-2.83	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.789211171	None	None	N
Y/T	0.9968	likely_pathogenic	0.9957	pathogenic	-2.425	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/V	0.8797	likely_pathogenic	0.8941	pathogenic	-0.876	Destabilizing	0.997	D	0.786	deleterious	None	None	None	None	N
Y/W	0.8762	likely_pathogenic	0.886	pathogenic	-0.009	Destabilizing	1.0	D	0.728	prob.delet.	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.