TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13693	41302;41303;41304	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
N2AB	12052	36379;36380;36381	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
N2A	11125	33598;33599;33600	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
N2B	4628	14107;14108;14109	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
Novex-1	4753	14482;14483;14484	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
Novex-2	4820	14683;14684;14685	chr2:178636650;178636649;178636648	chr2:179501377;179501376;179501375
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-87
• Domain position: 10
• Structural Position: 14
• Q(SASA): 0.747
• Predicted PPI site: I

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
I/S	None	None	0.001	N	0.367	0.258	0.619501705969	gnomAD-4.0.0	1.59222E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85989E-06	0	0
I/V	None	None	None	N	0.11	0.116	0.170165803431	gnomAD-4.0.0	6.36894E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14395E-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
I/A	0.5592	ambiguous	0.4221	ambiguous	-1.068	Destabilizing	None	N	0.245	neutral	None	None	None	None	I
I/C	0.8195	likely_pathogenic	0.7602	pathogenic	-0.913	Destabilizing	0.132	N	0.571	neutral	None	None	None	None	I
I/D	0.8617	likely_pathogenic	0.7712	pathogenic	-0.673	Destabilizing	0.008	N	0.335	neutral	None	None	None	None	I
I/E	0.702	likely_pathogenic	0.6064	pathogenic	-0.691	Destabilizing	0.002	N	0.411	neutral	None	None	None	None	I
I/F	0.3235	likely_benign	0.2531	benign	-0.664	Destabilizing	0.007	N	0.26	neutral	N	0.497788296	None	None	I
I/G	0.8421	likely_pathogenic	0.7288	pathogenic	-1.33	Destabilizing	0.003	N	0.383	neutral	None	None	None	None	I
I/H	0.6358	likely_pathogenic	0.5135	ambiguous	-0.453	Destabilizing	0.316	N	0.636	neutral	None	None	None	None	I
I/K	0.5501	ambiguous	0.4373	ambiguous	-0.878	Destabilizing	None	N	0.371	neutral	None	None	None	None	I
I/L	0.2234	likely_benign	0.1682	benign	-0.451	Destabilizing	None	N	0.112	neutral	N	0.471804842	None	None	I
I/M	0.2446	likely_benign	0.1737	benign	-0.572	Destabilizing	0.007	N	0.409	neutral	N	0.482542067	None	None	I
I/N	0.4541	ambiguous	0.3341	benign	-0.816	Destabilizing	0.006	N	0.361	neutral	N	0.463668937	None	None	I
I/P	0.9277	likely_pathogenic	0.861	pathogenic	-0.624	Destabilizing	0.008	N	0.343	neutral	None	None	None	None	I
I/Q	0.5839	likely_pathogenic	0.4568	ambiguous	-0.965	Destabilizing	0.004	N	0.359	neutral	None	None	None	None	I
I/R	0.452	ambiguous	0.366	ambiguous	-0.292	Destabilizing	0.002	N	0.345	neutral	None	None	None	None	I
I/S	0.4746	ambiguous	0.3526	ambiguous	-1.318	Destabilizing	0.001	N	0.367	neutral	N	0.445816768	None	None	I
I/T	0.2903	likely_benign	0.2199	benign	-1.221	Destabilizing	None	N	0.29	neutral	N	0.382177054	None	None	I
I/V	0.0671	likely_benign	0.0577	benign	-0.624	Destabilizing	None	N	0.11	neutral	N	0.35728742	None	None	I
I/W	0.9297	likely_pathogenic	0.8908	pathogenic	-0.728	Destabilizing	0.316	N	0.595	neutral	None	None	None	None	I
I/Y	0.6542	likely_pathogenic	0.6041	pathogenic	-0.503	Destabilizing	0.018	N	0.339	neutral	None	None	None	None	I

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.