TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24092	72499;72500;72501	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
N2AB	22451	67576;67577;67578	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
N2A	21524	64795;64796;64797	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
N2B	15027	45304;45305;45306	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
Novex-1	15152	45679;45680;45681	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
Novex-2	15219	45880;45881;45882	chr2:178573858;178573857;178573856	chr2:179438585;179438584;179438583
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-131
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.1582
• 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/T	None	None	0.939	N	0.469	0.251	0.267299060538	gnomAD-4.0.0	6.85447E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00969E-07	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
S/A	0.0959	likely_benign	0.1108	benign	-0.567	Destabilizing	0.046	N	0.278	neutral	N	0.386039965	None	None	N
S/C	0.1036	likely_benign	0.0996	benign	-1.128	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/D	0.9748	likely_pathogenic	0.9661	pathogenic	-2.299	Highly Destabilizing	0.976	D	0.603	neutral	None	None	None	None	N
S/E	0.9859	likely_pathogenic	0.9802	pathogenic	-2.189	Highly Destabilizing	0.953	D	0.59	neutral	None	None	None	None	N
S/F	0.8907	likely_pathogenic	0.9023	pathogenic	-0.946	Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
S/G	0.2367	likely_benign	0.2732	benign	-0.823	Destabilizing	0.91	D	0.457	neutral	None	None	None	None	N
S/H	0.9578	likely_pathogenic	0.9458	pathogenic	-1.29	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
S/I	0.5044	ambiguous	0.5129	ambiguous	0.026	Stabilizing	0.986	D	0.686	prob.neutral	None	None	None	None	N
S/K	0.9966	likely_pathogenic	0.9954	pathogenic	-0.592	Destabilizing	0.953	D	0.589	neutral	None	None	None	None	N
S/L	0.3959	ambiguous	0.4452	ambiguous	0.026	Stabilizing	0.939	D	0.622	neutral	N	0.457038846	None	None	N
S/M	0.6216	likely_pathogenic	0.6307	pathogenic	0.048	Stabilizing	0.999	D	0.668	neutral	None	None	None	None	N
S/N	0.727	likely_pathogenic	0.692	pathogenic	-1.336	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	N
S/P	0.7975	likely_pathogenic	0.8105	pathogenic	-0.141	Destabilizing	0.991	D	0.691	prob.neutral	N	0.469797499	None	None	N
S/Q	0.9746	likely_pathogenic	0.9667	pathogenic	-1.386	Destabilizing	0.993	D	0.67	neutral	None	None	None	None	N
S/R	0.9905	likely_pathogenic	0.9889	pathogenic	-0.578	Destabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
S/T	0.1509	likely_benign	0.1511	benign	-0.931	Destabilizing	0.939	D	0.469	neutral	N	0.450422305	None	None	N
S/V	0.3785	ambiguous	0.3954	ambiguous	-0.141	Destabilizing	0.973	D	0.657	neutral	None	None	None	None	N
S/W	0.9651	likely_pathogenic	0.9605	pathogenic	-1.224	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
S/Y	0.9059	likely_pathogenic	0.8961	pathogenic	-0.729	Destabilizing	0.998	D	0.693	prob.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.