TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6841	20746;20747;20748	chr2:178725801;178725800;178725799	chr2:179590528;179590527;179590526
N2AB	6524	19795;19796;19797	chr2:178725801;178725800;178725799	chr2:179590528;179590527;179590526
N2A	5597	17014;17015;17016	chr2:178725801;178725800;178725799	chr2:179590528;179590527;179590526
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-52
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.3856
• 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
S/I	rs769764362	0.049	0.771	N	0.539	0.396	0.63759658777	gnomAD-2.1.1	8.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
S/I	rs769764362	0.049	0.771	N	0.539	0.396	0.63759658777	gnomAD-4.0.0	2.748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.6103E-06	0	0
S/R	None	None	0.49	N	0.427	0.276	0.28722502521	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
S/A	0.0927	likely_benign	0.0981	benign	-0.493	Destabilizing	0.01	N	0.307	neutral	None	None	None	None	N
S/C	0.2075	likely_benign	0.1849	benign	-0.37	Destabilizing	0.932	D	0.466	neutral	D	0.527754324	None	None	N
S/D	0.6018	likely_pathogenic	0.6025	pathogenic	-0.376	Destabilizing	0.405	N	0.267	neutral	None	None	None	None	N
S/E	0.6357	likely_pathogenic	0.6636	pathogenic	-0.463	Destabilizing	0.488	N	0.249	neutral	None	None	None	None	N
S/F	0.1773	likely_benign	0.1731	benign	-0.988	Destabilizing	0.817	D	0.55	neutral	None	None	None	None	N
S/G	0.1343	likely_benign	0.1161	benign	-0.627	Destabilizing	0.282	N	0.259	neutral	D	0.526740366	None	None	N
S/H	0.4465	ambiguous	0.4255	ambiguous	-1.142	Destabilizing	0.948	D	0.477	neutral	None	None	None	None	N
S/I	0.192	likely_benign	0.1761	benign	-0.261	Destabilizing	0.771	D	0.539	neutral	N	0.511371589	None	None	N
S/K	0.7903	likely_pathogenic	0.789	pathogenic	-0.704	Destabilizing	0.033	N	0.133	neutral	None	None	None	None	N
S/L	0.1101	likely_benign	0.1127	benign	-0.261	Destabilizing	0.56	D	0.511	neutral	None	None	None	None	N
S/M	0.1969	likely_benign	0.1815	benign	0.137	Stabilizing	0.948	D	0.473	neutral	None	None	None	None	N
S/N	0.1677	likely_benign	0.1492	benign	-0.45	Destabilizing	0.057	N	0.285	neutral	N	0.497849237	None	None	N
S/P	0.8198	likely_pathogenic	0.8767	pathogenic	-0.309	Destabilizing	0.829	D	0.431	neutral	None	None	None	None	N
S/Q	0.5809	likely_pathogenic	0.5793	pathogenic	-0.785	Destabilizing	0.899	D	0.388	neutral	None	None	None	None	N
S/R	0.72	likely_pathogenic	0.7087	pathogenic	-0.389	Destabilizing	0.49	N	0.427	neutral	N	0.491088061	None	None	N
S/T	0.0796	likely_benign	0.0828	benign	-0.532	Destabilizing	None	N	0.105	neutral	N	0.499947048	None	None	N
S/V	0.1969	likely_benign	0.1932	benign	-0.309	Destabilizing	0.323	N	0.527	neutral	None	None	None	None	N
S/W	0.3851	ambiguous	0.3906	ambiguous	-0.95	Destabilizing	0.995	D	0.571	neutral	None	None	None	None	N
S/Y	0.2108	likely_benign	0.2156	benign	-0.702	Destabilizing	0.033	N	0.415	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.