TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32350	97273;97274;97275	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
N2AB	30709	92350;92351;92352	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
N2A	29782	89569;89570;89571	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
N2B	23285	70078;70079;70080	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
Novex-1	23410	70453;70454;70455	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
Novex-2	23477	70654;70655;70656	chr2:178542806;178542805;178542804	chr2:179407533;179407532;179407531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-154
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3034
• 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/P	None	None	0.989	N	0.319	0.241	0.245660935333	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
S/A	0.1591	likely_benign	0.1477	benign	-0.189	Destabilizing	0.267	N	0.32	neutral	N	0.455797927	None	None	N
S/C	0.2206	likely_benign	0.1978	benign	-0.26	Destabilizing	0.998	D	0.291	neutral	None	None	None	None	N
S/D	0.4108	ambiguous	0.4207	ambiguous	0.034	Stabilizing	0.971	D	0.349	neutral	None	None	None	None	N
S/E	0.685	likely_pathogenic	0.693	pathogenic	-0.073	Destabilizing	0.915	D	0.356	neutral	None	None	None	None	N
S/F	0.5189	ambiguous	0.4667	ambiguous	-0.835	Destabilizing	0.949	D	0.407	neutral	None	None	None	None	N
S/G	0.0851	likely_benign	0.0823	benign	-0.272	Destabilizing	0.915	D	0.298	neutral	None	None	None	None	N
S/H	0.5395	ambiguous	0.5263	ambiguous	-0.729	Destabilizing	0.998	D	0.291	neutral	None	None	None	None	N
S/I	0.4521	ambiguous	0.4104	ambiguous	-0.107	Destabilizing	0.525	D	0.311	neutral	None	None	None	None	N
S/K	0.803	likely_pathogenic	0.8003	pathogenic	-0.477	Destabilizing	0.915	D	0.315	neutral	None	None	None	None	N
S/L	0.1985	likely_benign	0.1716	benign	-0.107	Destabilizing	0.005	N	0.198	neutral	N	0.511277897	None	None	N
S/M	0.3008	likely_benign	0.2696	benign	0.029	Stabilizing	0.949	D	0.308	neutral	None	None	None	None	N
S/N	0.1393	likely_benign	0.1387	benign	-0.164	Destabilizing	0.971	D	0.4	neutral	None	None	None	None	N
S/P	0.6508	likely_pathogenic	0.6625	pathogenic	-0.107	Destabilizing	0.989	D	0.319	neutral	N	0.477261324	None	None	N
S/Q	0.6888	likely_pathogenic	0.6825	pathogenic	-0.417	Destabilizing	0.991	D	0.349	neutral	None	None	None	None	N
S/R	0.7982	likely_pathogenic	0.7963	pathogenic	-0.24	Destabilizing	0.991	D	0.333	neutral	None	None	None	None	N
S/T	0.0852	likely_benign	0.0797	benign	-0.265	Destabilizing	0.625	D	0.358	neutral	N	0.436356064	None	None	N
S/V	0.386	ambiguous	0.3456	ambiguous	-0.107	Destabilizing	0.016	N	0.263	neutral	None	None	None	None	N
S/W	0.6194	likely_pathogenic	0.5776	pathogenic	-0.894	Destabilizing	0.998	D	0.454	neutral	None	None	None	None	N
S/Y	0.4425	ambiguous	0.3873	ambiguous	-0.597	Destabilizing	0.991	D	0.411	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.