TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28684	86275;86276;86277	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
N2AB	27043	81352;81353;81354	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
N2A	26116	78571;78572;78573	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
N2B	19619	59080;59081;59082	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
Novex-1	19744	59455;59456;59457	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
Novex-2	19811	59656;59657;59658	chr2:178560082;178560081;178560080	chr2:179424809;179424808;179424807
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: Fn3-97
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.374
• 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
T/I	rs1703079044	None	0.032	N	0.312	0.145	0.263140351381	gnomAD-4.0.0	1.36849E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31873E-05	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	0.0933	likely_benign	0.0928	benign	-0.551	Destabilizing	0.489	N	0.524	neutral	N	0.494578829	None	None	I
T/C	0.3388	likely_benign	0.3272	benign	-0.318	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	I
T/D	0.4255	ambiguous	0.4344	ambiguous	0.218	Stabilizing	0.956	D	0.585	neutral	None	None	None	None	I
T/E	0.3063	likely_benign	0.3093	benign	0.168	Stabilizing	0.956	D	0.588	neutral	None	None	None	None	I
T/F	0.2039	likely_benign	0.2052	benign	-0.842	Destabilizing	0.956	D	0.751	deleterious	None	None	None	None	I
T/G	0.2529	likely_benign	0.2646	benign	-0.736	Destabilizing	0.86	D	0.597	neutral	None	None	None	None	I
T/H	0.2599	likely_benign	0.2538	benign	-1.083	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	I
T/I	0.111	likely_benign	0.1075	benign	-0.17	Destabilizing	0.032	N	0.312	neutral	N	0.512673124	None	None	I
T/K	0.2268	likely_benign	0.2278	benign	-0.497	Destabilizing	0.956	D	0.585	neutral	None	None	None	None	I
T/L	0.0684	likely_benign	0.0687	benign	-0.17	Destabilizing	0.514	D	0.517	neutral	None	None	None	None	I
T/M	0.0766	likely_benign	0.0767	benign	0.074	Stabilizing	0.988	D	0.669	neutral	None	None	None	None	I
T/N	0.1316	likely_benign	0.1359	benign	-0.272	Destabilizing	0.942	D	0.559	neutral	N	0.490971205	None	None	I
T/P	0.3742	ambiguous	0.3566	ambiguous	-0.266	Destabilizing	0.971	D	0.678	prob.neutral	N	0.510342907	None	None	I
T/Q	0.2286	likely_benign	0.2285	benign	-0.493	Destabilizing	0.978	D	0.674	neutral	None	None	None	None	I
T/R	0.1994	likely_benign	0.1923	benign	-0.273	Destabilizing	0.978	D	0.678	prob.neutral	None	None	None	None	I
T/S	0.1052	likely_benign	0.1105	benign	-0.549	Destabilizing	0.153	N	0.32	neutral	N	0.517558869	None	None	I
T/V	0.1043	likely_benign	0.1029	benign	-0.266	Destabilizing	0.514	D	0.5	neutral	None	None	None	None	I
T/W	0.5562	ambiguous	0.5434	ambiguous	-0.787	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
T/Y	0.2865	likely_benign	0.2809	benign	-0.541	Destabilizing	0.978	D	0.757	deleterious	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.