TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17070	51433;51434;51435	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
N2AB	15429	46510;46511;46512	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
N2A	14502	43729;43730;43731	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
N2B	8005	24238;24239;24240	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
Novex-1	8130	24613;24614;24615	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
Novex-2	8197	24814;24815;24816	chr2:178610318;178610317;178610316	chr2:179475045;179475044;179475043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-12
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4088
• 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
P/A	None	None	0.996	N	0.666	0.396	0.36076525451	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
P/A	0.087	likely_benign	0.0836	benign	-1.684	Destabilizing	0.996	D	0.666	neutral	N	0.475356673	None	None	N
P/C	0.6801	likely_pathogenic	0.6952	pathogenic	-1.018	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/D	0.7724	likely_pathogenic	0.7641	pathogenic	-1.857	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/E	0.4396	ambiguous	0.4332	ambiguous	-1.786	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/F	0.7156	likely_pathogenic	0.7173	pathogenic	-1.225	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/G	0.561	ambiguous	0.5477	ambiguous	-2.038	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/H	0.4383	ambiguous	0.4281	ambiguous	-1.477	Destabilizing	1.0	D	0.867	deleterious	D	0.63041492	None	None	N
P/I	0.3687	ambiguous	0.3369	benign	-0.771	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
P/K	0.4821	ambiguous	0.4369	ambiguous	-1.423	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/L	0.161	likely_benign	0.1646	benign	-0.771	Destabilizing	0.992	D	0.761	deleterious	D	0.596620026	None	None	N
P/M	0.3037	likely_benign	0.2961	benign	-0.654	Destabilizing	0.985	D	0.589	neutral	None	None	None	None	N
P/N	0.5849	likely_pathogenic	0.5699	pathogenic	-1.326	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/Q	0.2713	likely_benign	0.2576	benign	-1.42	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/R	0.423	ambiguous	0.4044	ambiguous	-0.952	Destabilizing	0.999	D	0.877	deleterious	N	0.514097196	None	None	N
P/S	0.2368	likely_benign	0.2297	benign	-1.794	Destabilizing	0.999	D	0.775	deleterious	D	0.575475538	None	None	N
P/T	0.1922	likely_benign	0.1799	benign	-1.606	Destabilizing	0.999	D	0.795	deleterious	D	0.560953986	None	None	N
P/V	0.2531	likely_benign	0.2305	benign	-1.046	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
P/W	0.9139	likely_pathogenic	0.9186	pathogenic	-1.459	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/Y	0.7099	likely_pathogenic	0.7238	pathogenic	-1.156	Destabilizing	1.0	D	0.873	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.