TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15398	46417;46418;46419	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
N2AB	13757	41494;41495;41496	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
N2A	12830	38713;38714;38715	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
N2B	6333	19222;19223;19224	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
Novex-1	6458	19597;19598;19599	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
Novex-2	6525	19798;19799;19800	chr2:178620329;178620328;178620327	chr2:179485056;179485055;179485054
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-106
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2317
• 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/K	rs1405135300	None	0.003	N	0.117	0.172	0.240491677333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1405135300	None	0.003	N	0.117	0.172	0.240491677333	gnomAD-4.0.0	2.62404E-06	None	None	None	None	N	None	1.7066E-05	0	None	0	0	None	0	0	0	0	2.91562E-05
E/V	rs978970349	None	0.101	N	0.459	0.192	0.394685799254	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.28E-06	0
E/V	rs978970349	None	0.101	N	0.459	0.192	0.394685799254	gnomAD-4.0.0	1.47524E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.64849E-05	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	0.1561	likely_benign	0.2022	benign	-0.312	Destabilizing	0.047	N	0.261	neutral	N	0.502657247	None	None	N
E/C	0.8183	likely_pathogenic	0.8736	pathogenic	-0.126	Destabilizing	0.983	D	0.515	neutral	None	None	None	None	N
E/D	0.2207	likely_benign	0.264	benign	-0.388	Destabilizing	0.183	N	0.296	neutral	N	0.511589718	None	None	N
E/F	0.7673	likely_pathogenic	0.8344	pathogenic	-0.082	Destabilizing	0.716	D	0.553	neutral	None	None	None	None	N
E/G	0.2048	likely_benign	0.2453	benign	-0.531	Destabilizing	0.001	N	0.256	neutral	D	0.543664291	None	None	N
E/H	0.3907	ambiguous	0.4619	ambiguous	0.183	Stabilizing	0.836	D	0.417	neutral	None	None	None	None	N
E/I	0.3777	ambiguous	0.4814	ambiguous	0.234	Stabilizing	0.264	N	0.531	neutral	None	None	None	None	N
E/K	0.1062	likely_benign	0.1325	benign	0.298	Stabilizing	0.003	N	0.117	neutral	N	0.450956178	None	None	N
E/L	0.35	ambiguous	0.4551	ambiguous	0.234	Stabilizing	0.129	N	0.411	neutral	None	None	None	None	N
E/M	0.4457	ambiguous	0.5501	ambiguous	0.222	Stabilizing	0.061	N	0.305	neutral	None	None	None	None	N
E/N	0.2958	likely_benign	0.4037	ambiguous	-0.086	Destabilizing	0.228	N	0.358	neutral	None	None	None	None	N
E/P	0.7372	likely_pathogenic	0.8523	pathogenic	0.073	Stabilizing	0.593	D	0.436	neutral	None	None	None	None	N
E/Q	0.0881	likely_benign	0.114	benign	-0.03	Destabilizing	0.003	N	0.135	neutral	N	0.482006266	None	None	N
E/R	0.1525	likely_benign	0.1747	benign	0.564	Stabilizing	0.129	N	0.351	neutral	None	None	None	None	N
E/S	0.2141	likely_benign	0.2822	benign	-0.246	Destabilizing	0.012	N	0.151	neutral	None	None	None	None	N
E/T	0.2126	likely_benign	0.2917	benign	-0.064	Destabilizing	0.129	N	0.413	neutral	None	None	None	None	N
E/V	0.2304	likely_benign	0.2895	benign	0.073	Stabilizing	0.101	N	0.459	neutral	N	0.512994744	None	None	N
E/W	0.8806	likely_pathogenic	0.9113	pathogenic	0.089	Stabilizing	0.983	D	0.535	neutral	None	None	None	None	N
E/Y	0.6562	likely_pathogenic	0.7197	pathogenic	0.171	Stabilizing	0.94	D	0.541	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.