TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27422	82489;82490;82491	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
N2AB	25781	77566;77567;77568	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
N2A	24854	74785;74786;74787	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
N2B	18357	55294;55295;55296	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
Novex-1	18482	55669;55670;55671	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
Novex-2	18549	55870;55871;55872	chr2:178563868;178563867;178563866	chr2:179428595;179428594;179428593
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: Fn3-87
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.6654
• 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/A	rs760304866	-0.486	None	N	0.083	0.075	0.17258766438	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/A	rs760304866	-0.486	None	N	0.083	0.075	0.17258766438	gnomAD-4.0.0	1.75048E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.14426E-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
T/A	0.0593	likely_benign	0.0614	benign	-0.62	Destabilizing	None	N	0.083	neutral	N	0.413698209	None	None	N
T/C	0.2967	likely_benign	0.3047	benign	-0.363	Destabilizing	0.676	D	0.352	neutral	None	None	None	None	N
T/D	0.2702	likely_benign	0.2904	benign	-0.024	Destabilizing	0.038	N	0.316	neutral	None	None	None	None	N
T/E	0.2216	likely_benign	0.2346	benign	-0.059	Destabilizing	0.038	N	0.302	neutral	None	None	None	None	N
T/F	0.2301	likely_benign	0.2468	benign	-0.812	Destabilizing	0.356	N	0.363	neutral	None	None	None	None	N
T/G	0.129	likely_benign	0.1273	benign	-0.836	Destabilizing	0.016	N	0.268	neutral	None	None	None	None	N
T/H	0.2028	likely_benign	0.2082	benign	-1.096	Destabilizing	0.214	N	0.335	neutral	None	None	None	None	N
T/I	0.1697	likely_benign	0.1759	benign	-0.152	Destabilizing	0.171	N	0.406	neutral	N	0.492908354	None	None	N
T/K	0.1602	likely_benign	0.1729	benign	-0.628	Destabilizing	0.038	N	0.316	neutral	None	None	None	None	N
T/L	0.0835	likely_benign	0.0876	benign	-0.152	Destabilizing	0.072	N	0.295	neutral	None	None	None	None	N
T/M	0.0862	likely_benign	0.0906	benign	0.084	Stabilizing	0.628	D	0.361	neutral	None	None	None	None	N
T/N	0.095	likely_benign	0.0928	benign	-0.443	Destabilizing	None	N	0.158	neutral	N	0.460260004	None	None	N
T/P	0.0763	likely_benign	0.0803	benign	-0.276	Destabilizing	None	N	0.193	neutral	N	0.42709158	None	None	N
T/Q	0.1847	likely_benign	0.1897	benign	-0.647	Destabilizing	0.214	N	0.413	neutral	None	None	None	None	N
T/R	0.147	likely_benign	0.1612	benign	-0.338	Destabilizing	0.214	N	0.403	neutral	None	None	None	None	N
T/S	0.076	likely_benign	0.0753	benign	-0.707	Destabilizing	None	N	0.095	neutral	N	0.377913554	None	None	N
T/V	0.1191	likely_benign	0.1219	benign	-0.276	Destabilizing	0.072	N	0.198	neutral	None	None	None	None	N
T/W	0.5143	ambiguous	0.5664	pathogenic	-0.758	Destabilizing	0.864	D	0.428	neutral	None	None	None	None	N
T/Y	0.24	likely_benign	0.2674	benign	-0.526	Destabilizing	0.356	N	0.362	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.