TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21279	64060;64061;64062	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
N2AB	19638	59137;59138;59139	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
N2A	18711	56356;56357;56358	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
N2B	12214	36865;36866;36867	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
Novex-1	12339	37240;37241;37242	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
Novex-2	12406	37441;37442;37443	chr2:178587376;178587375;178587374	chr2:179452103;179452102;179452101
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-42
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.3075
• 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
T/S	rs1276354995	-0.684	0.103	N	0.153	0.101	0.110078149338	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
T/S	rs1276354995	-0.684	0.103	N	0.153	0.101	0.110078149338	gnomAD-4.0.0	1.6145E-06	None	None	None	None	N	None	0	2.31342E-05	None	0	0	None	0	0	0	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
T/A	0.1887	likely_benign	0.2036	benign	-0.458	Destabilizing	0.64	D	0.467	neutral	N	0.471501051	None	None	N
T/C	0.5545	ambiguous	0.5833	pathogenic	-0.559	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
T/D	0.5233	ambiguous	0.5774	pathogenic	-1.574	Destabilizing	0.851	D	0.423	neutral	None	None	None	None	N
T/E	0.5315	ambiguous	0.5827	pathogenic	-1.565	Destabilizing	0.919	D	0.416	neutral	None	None	None	None	N
T/F	0.5727	likely_pathogenic	0.6227	pathogenic	-0.82	Destabilizing	0.996	D	0.521	neutral	None	None	None	None	N
T/G	0.252	likely_benign	0.271	benign	-0.687	Destabilizing	0.851	D	0.431	neutral	None	None	None	None	N
T/H	0.4159	ambiguous	0.459	ambiguous	-1.177	Destabilizing	0.997	D	0.512	neutral	None	None	None	None	N
T/I	0.5852	likely_pathogenic	0.6397	pathogenic	0.057	Stabilizing	0.984	D	0.429	neutral	N	0.498443624	None	None	N
T/K	0.2636	likely_benign	0.2872	benign	-0.707	Destabilizing	0.919	D	0.407	neutral	None	None	None	None	N
T/L	0.1971	likely_benign	0.227	benign	0.057	Stabilizing	0.919	D	0.414	neutral	None	None	None	None	N
T/M	0.1587	likely_benign	0.1848	benign	0.495	Stabilizing	0.999	D	0.441	neutral	None	None	None	None	N
T/N	0.1568	likely_benign	0.1774	benign	-0.998	Destabilizing	0.103	N	0.271	neutral	N	0.4864866	None	None	N
T/P	0.7498	likely_pathogenic	0.7694	pathogenic	-0.084	Destabilizing	0.984	D	0.431	neutral	N	0.494658189	None	None	N
T/Q	0.2824	likely_benign	0.3095	benign	-1.27	Destabilizing	0.988	D	0.442	neutral	None	None	None	None	N
T/R	0.2565	likely_benign	0.2748	benign	-0.425	Destabilizing	0.976	D	0.435	neutral	None	None	None	None	N
T/S	0.1159	likely_benign	0.1252	benign	-0.994	Destabilizing	0.103	N	0.153	neutral	N	0.472959943	None	None	N
T/V	0.3965	ambiguous	0.4387	ambiguous	-0.084	Destabilizing	0.919	D	0.435	neutral	None	None	None	None	N
T/W	0.84	likely_pathogenic	0.8642	pathogenic	-0.913	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
T/Y	0.5855	likely_pathogenic	0.6365	pathogenic	-0.538	Destabilizing	0.996	D	0.513	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.