TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29107	87544;87545;87546	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
N2AB	27466	82621;82622;82623	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
N2A	26539	79840;79841;79842	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
N2B	20042	60349;60350;60351	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
Novex-1	20167	60724;60725;60726	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
Novex-2	20234	60925;60926;60927	chr2:178558035;178558034;178558033	chr2:179422762;179422761;179422760
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-145
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.14
• 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/N	None	None	0.999	N	0.654	0.339	0.372268306217	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99416E-07	1.15931E-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	0.0708	likely_benign	0.0642	benign	-0.441	Destabilizing	0.98	D	0.469	neutral	None	None	None	None	N
S/C	0.1041	likely_benign	0.0834	benign	-1.002	Destabilizing	0.391	N	0.483	neutral	N	0.463698246	None	None	N
S/D	0.9781	likely_pathogenic	0.9675	pathogenic	-2.217	Highly Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
S/E	0.9842	likely_pathogenic	0.9786	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/F	0.9106	likely_pathogenic	0.8421	pathogenic	-0.757	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
S/G	0.1892	likely_benign	0.1539	benign	-0.684	Destabilizing	0.994	D	0.557	neutral	N	0.490567855	None	None	N
S/H	0.9749	likely_pathogenic	0.9599	pathogenic	-1.162	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
S/I	0.3617	ambiguous	0.3231	benign	0.109	Stabilizing	0.998	D	0.736	prob.delet.	N	0.496362451	None	None	N
S/K	0.9972	likely_pathogenic	0.9957	pathogenic	-0.654	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
S/L	0.3352	likely_benign	0.2443	benign	0.109	Stabilizing	0.992	D	0.677	prob.neutral	None	None	None	None	N
S/M	0.4779	ambiguous	0.377	ambiguous	0.126	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
S/N	0.7639	likely_pathogenic	0.6858	pathogenic	-1.258	Destabilizing	0.999	D	0.654	neutral	N	0.490567855	None	None	N
S/P	0.8182	likely_pathogenic	0.7539	pathogenic	-0.043	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
S/Q	0.9817	likely_pathogenic	0.9737	pathogenic	-1.38	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
S/R	0.9942	likely_pathogenic	0.9918	pathogenic	-0.563	Destabilizing	0.999	D	0.741	deleterious	N	0.490567855	None	None	N
S/T	0.1062	likely_benign	0.0873	benign	-0.88	Destabilizing	0.994	D	0.561	neutral	N	0.505640869	None	None	N
S/V	0.2718	likely_benign	0.2353	benign	-0.043	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
S/W	0.9667	likely_pathogenic	0.9431	pathogenic	-1.005	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
S/Y	0.9128	likely_pathogenic	0.8613	pathogenic	-0.535	Destabilizing	1.0	D	0.728	prob.delet.	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.