TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6539	19840;19841;19842	chr2:178728209;178728208;178728207	chr2:179592936;179592935;179592934
N2AB	6222	18889;18890;18891	chr2:178728209;178728208;178728207	chr2:179592936;179592935;179592934
N2A	5295	16108;16109;16110	chr2:178728209;178728208;178728207	chr2:179592936;179592935;179592934
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-49
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.4143
• 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
E/D	None	None	None	N	0.308	0.077	0.0716867268079	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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	0.1548	likely_benign	0.1729	benign	-0.939	Destabilizing	0.124	N	0.563	neutral	D	0.52376527	None	None	N
E/C	0.8314	likely_pathogenic	0.8871	pathogenic	-0.686	Destabilizing	0.968	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.158	likely_benign	0.1831	benign	-1.503	Destabilizing	None	N	0.308	neutral	N	0.4968881	None	None	N
E/F	0.6379	likely_pathogenic	0.7132	pathogenic	-0.786	Destabilizing	0.726	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.2821	likely_benign	0.3207	benign	-1.324	Destabilizing	0.22	N	0.607	neutral	N	0.495696417	None	None	N
E/H	0.366	ambiguous	0.4599	ambiguous	-1.14	Destabilizing	0.909	D	0.618	neutral	None	None	None	None	N
E/I	0.2615	likely_benign	0.315	benign	0.119	Stabilizing	0.567	D	0.734	prob.delet.	None	None	None	None	N
E/K	0.1869	likely_benign	0.2386	benign	-1.058	Destabilizing	0.22	N	0.569	neutral	N	0.463698246	None	None	N
E/L	0.3151	likely_benign	0.3717	ambiguous	0.119	Stabilizing	0.396	N	0.691	prob.neutral	None	None	None	None	N
E/M	0.3721	ambiguous	0.4237	ambiguous	0.678	Stabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
E/N	0.2957	likely_benign	0.3628	ambiguous	-1.383	Destabilizing	0.157	N	0.575	neutral	None	None	None	None	N
E/P	0.9439	likely_pathogenic	0.9633	pathogenic	-0.213	Destabilizing	0.726	D	0.681	prob.neutral	None	None	None	None	N
E/Q	0.1343	likely_benign	0.1593	benign	-1.192	Destabilizing	0.497	N	0.624	neutral	N	0.493039718	None	None	N
E/R	0.2671	likely_benign	0.3348	benign	-0.961	Destabilizing	0.567	D	0.615	neutral	None	None	None	None	N
E/S	0.2276	likely_benign	0.2682	benign	-1.848	Destabilizing	0.157	N	0.571	neutral	None	None	None	None	N
E/T	0.2028	likely_benign	0.2296	benign	-1.511	Destabilizing	0.011	N	0.408	neutral	None	None	None	None	N
E/V	0.1567	likely_benign	0.1843	benign	-0.213	Destabilizing	0.331	N	0.664	neutral	N	0.477627549	None	None	N
E/W	0.8315	likely_pathogenic	0.8795	pathogenic	-0.794	Destabilizing	0.968	D	0.673	neutral	None	None	None	None	N
E/Y	0.5243	ambiguous	0.6368	pathogenic	-0.589	Destabilizing	0.89	D	0.716	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.