TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30860	92803;92804;92805	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
N2AB	29219	87880;87881;87882	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
N2A	28292	85099;85100;85101	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
N2B	21795	65608;65609;65610	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
Novex-1	21920	65983;65984;65985	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
Novex-2	21987	66184;66185;66186	chr2:178549048;178549047;178549046	chr2:179413775;179413774;179413773
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-113
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0722
• 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
M/I	None	None	0.004	N	0.346	0.178	0.554116578535	gnomAD-4.0.0	6.84174E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99428E-07	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
M/A	0.571	likely_pathogenic	0.5433	ambiguous	-2.093	Highly Destabilizing	0.4	N	0.737	prob.delet.	None	None	None	None	N
M/C	0.7439	likely_pathogenic	0.729	pathogenic	-1.943	Destabilizing	0.992	D	0.788	deleterious	None	None	None	None	N
M/D	0.9833	likely_pathogenic	0.9763	pathogenic	-2.089	Highly Destabilizing	0.972	D	0.839	deleterious	None	None	None	None	N
M/E	0.8138	likely_pathogenic	0.7622	pathogenic	-1.84	Destabilizing	0.972	D	0.813	deleterious	None	None	None	None	N
M/F	0.4698	ambiguous	0.4011	ambiguous	-0.712	Destabilizing	0.617	D	0.799	deleterious	None	None	None	None	N
M/G	0.8278	likely_pathogenic	0.8195	pathogenic	-2.574	Highly Destabilizing	0.92	D	0.814	deleterious	None	None	None	None	N
M/H	0.7641	likely_pathogenic	0.7025	pathogenic	-2.336	Highly Destabilizing	0.992	D	0.797	deleterious	None	None	None	None	N
M/I	0.5757	likely_pathogenic	0.4849	ambiguous	-0.698	Destabilizing	0.004	N	0.346	neutral	N	0.453928678	None	None	N
M/K	0.2487	likely_benign	0.19	benign	-1.268	Destabilizing	0.712	D	0.797	deleterious	N	0.412890132	None	None	N
M/L	0.2913	likely_benign	0.262	benign	-0.698	Destabilizing	0.016	N	0.459	neutral	N	0.498775533	None	None	N
M/N	0.8565	likely_pathogenic	0.8111	pathogenic	-1.723	Destabilizing	0.972	D	0.819	deleterious	None	None	None	None	N
M/P	0.9979	likely_pathogenic	0.9974	pathogenic	-1.148	Destabilizing	0.972	D	0.814	deleterious	None	None	None	None	N
M/Q	0.3991	ambiguous	0.3498	ambiguous	-1.374	Destabilizing	0.972	D	0.792	deleterious	None	None	None	None	N
M/R	0.3393	likely_benign	0.2792	benign	-1.459	Destabilizing	0.963	D	0.817	deleterious	N	0.4618948	None	None	N
M/S	0.6601	likely_pathogenic	0.6344	pathogenic	-2.215	Highly Destabilizing	0.766	D	0.776	deleterious	None	None	None	None	N
M/T	0.4984	ambiguous	0.4191	ambiguous	-1.839	Destabilizing	0.549	D	0.769	deleterious	N	0.519094877	None	None	N
M/V	0.1979	likely_benign	0.172	benign	-1.148	Destabilizing	0.036	N	0.498	neutral	N	0.466991189	None	None	N
M/W	0.8537	likely_pathogenic	0.8159	pathogenic	-1.111	Destabilizing	0.992	D	0.775	deleterious	None	None	None	None	N
M/Y	0.6582	likely_pathogenic	0.5874	pathogenic	-1.053	Destabilizing	0.92	D	0.824	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.