TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1915	5968;5969;5970	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
N2AB	1915	5968;5969;5970	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
N2A	1915	5968;5969;5970	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
N2B	1869	5830;5831;5832	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
Novex-1	1869	5830;5831;5832	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
Novex-2	1869	5830;5831;5832	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846
Novex-3	1915	5968;5969;5970	chr2:178776121;178776120;178776119	chr2:179640848;179640847;179640846

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-9
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.3674
• 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
E/K	rs375388374	-0.518	0.994	N	0.62	0.436	None	gnomAD-2.1.1	7.96E-06	None	None	None	None	I	None	1.23062E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs375388374	-0.518	0.994	N	0.62	0.436	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs375388374	-0.518	0.994	N	0.62	0.436	None	gnomAD-4.0.0	2.56104E-06	None	None	None	None	I	None	3.38158E-05	0	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
E/A	0.4899	ambiguous	0.6125	pathogenic	-0.748	Destabilizing	0.994	D	0.653	neutral	N	0.513183643	None	None	I
E/C	0.983	likely_pathogenic	0.9899	pathogenic	-0.372	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/D	0.3263	likely_benign	0.3991	ambiguous	-1.094	Destabilizing	0.104	N	0.211	neutral	N	0.514349462	None	None	I
E/F	0.9727	likely_pathogenic	0.9831	pathogenic	-0.569	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/G	0.6324	likely_pathogenic	0.7323	pathogenic	-1.071	Destabilizing	0.994	D	0.72	prob.delet.	D	0.635226582	None	None	I
E/H	0.9096	likely_pathogenic	0.9495	pathogenic	-0.937	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
E/I	0.8076	likely_pathogenic	0.869	pathogenic	0.116	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
E/K	0.6349	likely_pathogenic	0.7688	pathogenic	-0.668	Destabilizing	0.994	D	0.62	neutral	N	0.503072274	None	None	I
E/L	0.8836	likely_pathogenic	0.9268	pathogenic	0.116	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
E/M	0.8699	likely_pathogenic	0.9127	pathogenic	0.563	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
E/N	0.6909	likely_pathogenic	0.7744	pathogenic	-0.934	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	I
E/P	0.9979	likely_pathogenic	0.9992	pathogenic	-0.15	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/Q	0.4175	ambiguous	0.5199	ambiguous	-0.838	Destabilizing	0.998	D	0.697	prob.neutral	N	0.509381845	None	None	I
E/R	0.8051	likely_pathogenic	0.886	pathogenic	-0.507	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
E/S	0.5075	ambiguous	0.6069	pathogenic	-1.228	Destabilizing	0.992	D	0.627	neutral	None	None	None	None	I
E/T	0.5866	likely_pathogenic	0.7051	pathogenic	-0.975	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
E/V	0.5947	likely_pathogenic	0.6965	pathogenic	-0.15	Destabilizing	0.999	D	0.819	deleterious	N	0.512365459	None	None	I
E/W	0.9937	likely_pathogenic	0.9966	pathogenic	-0.466	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
E/Y	0.96	likely_pathogenic	0.9767	pathogenic	-0.368	Destabilizing	1.0	D	0.827	deleterious	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.