TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20167	60724;60725;60726	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
N2AB	18526	55801;55802;55803	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
N2A	17599	53020;53021;53022	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
N2B	11102	33529;33530;33531	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
Novex-1	11227	33904;33905;33906	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
Novex-2	11294	34105;34106;34107	chr2:178591226;178591225;178591224	chr2:179455953;179455952;179455951
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: Ig-120
• Domain position: 88
• Structural Position: 175
• Q(SASA): 0.4102
• 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/I	None	None	1.0	D	0.816	0.455	0.642232531769	gnomAD-4.0.0	6.84356E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99622E-07	0	0
T/P	None	None	1.0	D	0.798	0.557	0.66854072215	gnomAD-4.0.0	1.59204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-06	0	0
T/S	rs2050127510	None	0.999	D	0.577	0.421	0.508696012846	gnomAD-4.0.0	1.36871E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79924E-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
T/A	0.135	likely_benign	0.1573	benign	-0.895	Destabilizing	0.999	D	0.572	neutral	N	0.50153254	None	None	N
T/C	0.5368	ambiguous	0.5977	pathogenic	-0.623	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
T/D	0.5692	likely_pathogenic	0.6186	pathogenic	-0.436	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
T/E	0.455	ambiguous	0.5304	ambiguous	-0.374	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
T/F	0.3859	ambiguous	0.4541	ambiguous	-0.691	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/G	0.5352	ambiguous	0.5691	pathogenic	-1.22	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/H	0.2759	likely_benign	0.3305	benign	-1.4	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
T/I	0.1869	likely_benign	0.2324	benign	-0.098	Destabilizing	1.0	D	0.816	deleterious	D	0.526037571	None	None	N
T/K	0.2618	likely_benign	0.3151	benign	-0.788	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
T/L	0.1308	likely_benign	0.1532	benign	-0.098	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
T/M	0.0977	likely_benign	0.1139	benign	0.046	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/N	0.1462	likely_benign	0.1726	benign	-0.907	Destabilizing	1.0	D	0.788	deleterious	D	0.526498931	None	None	N
T/P	0.8135	likely_pathogenic	0.8403	pathogenic	-0.33	Destabilizing	1.0	D	0.798	deleterious	D	0.536161342	None	None	N
T/Q	0.2705	likely_benign	0.3083	benign	-0.955	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
T/R	0.2392	likely_benign	0.2865	benign	-0.652	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/S	0.1667	likely_benign	0.1921	benign	-1.206	Destabilizing	0.999	D	0.577	neutral	D	0.526786933	None	None	N
T/V	0.1559	likely_benign	0.1837	benign	-0.33	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
T/W	0.7382	likely_pathogenic	0.77	pathogenic	-0.66	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/Y	0.392	ambiguous	0.4271	ambiguous	-0.413	Destabilizing	1.0	D	0.803	deleterious	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.