TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14247	42964;42965;42966	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
N2AB	12606	38041;38042;38043	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
N2A	11679	35260;35261;35262	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
N2B	5182	15769;15770;15771	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
Novex-1	5307	16144;16145;16146	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
Novex-2	5374	16345;16346;16347	chr2:178633620;178633619;178633618	chr2:179498347;179498346;179498345
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-93
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.3734
• 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	rs1017956154	None	0.001	N	0.113	0.064	0.132336055621	gnomAD-4.0.0	6.84493E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99628E-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
E/A	0.2108	likely_benign	0.1585	benign	-0.729	Destabilizing	0.007	N	0.226	neutral	N	0.450327924	None	None	N
E/C	0.9231	likely_pathogenic	0.8699	pathogenic	-0.327	Destabilizing	0.987	D	0.437	neutral	None	None	None	None	N
E/D	0.0853	likely_benign	0.0773	benign	-0.84	Destabilizing	0.001	N	0.113	neutral	N	0.43253157	None	None	N
E/F	0.8071	likely_pathogenic	0.7142	pathogenic	-0.376	Destabilizing	0.953	D	0.435	neutral	None	None	None	None	N
E/G	0.2782	likely_benign	0.1975	benign	-1.035	Destabilizing	0.521	D	0.391	neutral	D	0.59794415	None	None	N
E/H	0.6173	likely_pathogenic	0.5305	ambiguous	-0.559	Destabilizing	0.953	D	0.383	neutral	None	None	None	None	N
E/I	0.4135	ambiguous	0.2985	benign	0.082	Stabilizing	0.91	D	0.451	neutral	None	None	None	None	N
E/K	0.3	likely_benign	0.2146	benign	-0.4	Destabilizing	0.028	N	0.157	neutral	N	0.444011026	None	None	N
E/L	0.5411	ambiguous	0.4257	ambiguous	0.082	Stabilizing	0.59	D	0.452	neutral	None	None	None	None	N
E/M	0.5865	likely_pathogenic	0.4556	ambiguous	0.424	Stabilizing	0.996	D	0.407	neutral	None	None	None	None	N
E/N	0.2315	likely_benign	0.1812	benign	-0.77	Destabilizing	0.59	D	0.261	neutral	None	None	None	None	N
E/P	0.6406	likely_pathogenic	0.6023	pathogenic	-0.167	Destabilizing	0.854	D	0.415	neutral	None	None	None	None	N
E/Q	0.2449	likely_benign	0.2002	benign	-0.676	Destabilizing	0.078	N	0.22	neutral	N	0.440553682	None	None	N
E/R	0.4756	ambiguous	0.3785	ambiguous	-0.151	Destabilizing	0.59	D	0.335	neutral	None	None	None	None	N
E/S	0.2305	likely_benign	0.1787	benign	-1.011	Destabilizing	0.373	N	0.297	neutral	None	None	None	None	N
E/T	0.2179	likely_benign	0.1767	benign	-0.767	Destabilizing	0.742	D	0.355	neutral	None	None	None	None	N
E/V	0.2639	likely_benign	0.1945	benign	-0.167	Destabilizing	0.521	D	0.435	neutral	N	0.450438219	None	None	N
E/W	0.9389	likely_pathogenic	0.902	pathogenic	-0.172	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
E/Y	0.7072	likely_pathogenic	0.5971	pathogenic	-0.148	Destabilizing	0.984	D	0.427	neutral	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.