TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33006	99241;99242;99243	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
N2AB	31365	94318;94319;94320	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
N2A	30438	91537;91538;91539	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
N2B	23941	72046;72047;72048	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
Novex-1	24066	72421;72422;72423	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
Novex-2	24133	72622;72623;72624	chr2:178538813;178538812;178538811	chr2:179403540;179403539;179403538
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: Fn3-129
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4283
• 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	rs201931674	0.264	0.978	N	0.503	0.344	0.269111216191	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
E/K	rs201931674	0.264	0.978	N	0.503	0.344	0.269111216191	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs201931674	0.264	0.978	N	0.503	0.344	0.269111216191	gnomAD-4.0.0	1.11785E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.56627E-05	0	1.44343E-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	0.2286	likely_benign	0.2819	benign	-0.52	Destabilizing	0.989	D	0.587	neutral	N	0.492391066	None	None	N
E/C	0.8561	likely_pathogenic	0.8864	pathogenic	-0.332	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/D	0.1263	likely_benign	0.138	benign	-0.552	Destabilizing	0.054	N	0.193	neutral	N	0.49121763	None	None	N
E/F	0.8194	likely_pathogenic	0.8661	pathogenic	-0.046	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
E/G	0.2432	likely_benign	0.3161	benign	-0.796	Destabilizing	0.978	D	0.633	neutral	N	0.480763307	None	None	N
E/H	0.4855	ambiguous	0.5258	ambiguous	0.09	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	N
E/I	0.4899	ambiguous	0.5447	ambiguous	0.201	Stabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
E/K	0.2303	likely_benign	0.2686	benign	0.011	Stabilizing	0.978	D	0.503	neutral	N	0.431955895	None	None	N
E/L	0.5227	ambiguous	0.5892	pathogenic	0.201	Stabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
E/M	0.5782	likely_pathogenic	0.6437	pathogenic	0.249	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/N	0.2433	likely_benign	0.2879	benign	-0.504	Destabilizing	0.983	D	0.545	neutral	None	None	None	None	N
E/P	0.9377	likely_pathogenic	0.9592	pathogenic	-0.018	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
E/Q	0.1626	likely_benign	0.18	benign	-0.411	Destabilizing	0.989	D	0.545	neutral	N	0.442962323	None	None	N
E/R	0.3519	ambiguous	0.3953	ambiguous	0.349	Stabilizing	0.998	D	0.594	neutral	None	None	None	None	N
E/S	0.2261	likely_benign	0.2739	benign	-0.69	Destabilizing	0.983	D	0.495	neutral	None	None	None	None	N
E/T	0.2507	likely_benign	0.2943	benign	-0.46	Destabilizing	0.992	D	0.664	neutral	None	None	None	None	N
E/V	0.2939	likely_benign	0.3395	benign	-0.018	Destabilizing	0.999	D	0.705	prob.neutral	N	0.487907966	None	None	N
E/W	0.9279	likely_pathogenic	0.9481	pathogenic	0.203	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/Y	0.7017	likely_pathogenic	0.7654	pathogenic	0.212	Stabilizing	0.999	D	0.807	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.