TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33086	99481;99482;99483	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
N2AB	31445	94558;94559;94560	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
N2A	30518	91777;91778;91779	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
N2B	24021	72286;72287;72288	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
Novex-1	24146	72661;72662;72663	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
Novex-2	24213	72862;72863;72864	chr2:178538573;178538572;178538571	chr2:179403300;179403299;179403298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-129
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.6891
• 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
R/S	None	None	0.999	N	0.795	0.338	0.264547087235	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
R/A	0.8964	likely_pathogenic	0.8911	pathogenic	-0.503	Destabilizing	0.998	D	0.705	prob.delet.	None	None	None	None	N
R/C	0.608	likely_pathogenic	0.5647	pathogenic	-0.55	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
R/D	0.9633	likely_pathogenic	0.9614	pathogenic	-0.041	Destabilizing	0.999	D	0.736	deleterious	None	None	None	None	N
R/E	0.8439	likely_pathogenic	0.8233	pathogenic	0.112	Stabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
R/F	0.9131	likely_pathogenic	0.9097	pathogenic	-0.227	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
R/G	0.7636	likely_pathogenic	0.7739	pathogenic	-0.822	Destabilizing	0.999	D	0.685	prob.delet.	N	0.497018599	None	None	N
R/H	0.4075	ambiguous	0.3911	ambiguous	-1.231	Destabilizing	0.999	D	0.86	deleterious	None	None	None	None	N
R/I	0.7904	likely_pathogenic	0.7745	pathogenic	0.355	Stabilizing	0.999	D	0.738	deleterious	N	0.50123234	None	None	N
R/K	0.2772	likely_benign	0.2696	benign	-0.41	Destabilizing	0.994	D	0.675	prob.neutral	N	0.454515829	None	None	N
R/L	0.6894	likely_pathogenic	0.6882	pathogenic	0.355	Stabilizing	0.999	D	0.685	prob.delet.	None	None	None	None	N
R/M	0.7967	likely_pathogenic	0.7932	pathogenic	-0.243	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
R/N	0.9314	likely_pathogenic	0.9326	pathogenic	-0.21	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
R/P	0.8762	likely_pathogenic	0.8772	pathogenic	0.09	Stabilizing	0.999	D	0.727	deleterious	None	None	None	None	N
R/Q	0.3434	ambiguous	0.3335	benign	-0.21	Destabilizing	0.999	D	0.868	deleterious	None	None	None	None	N
R/S	0.9302	likely_pathogenic	0.926	pathogenic	-0.796	Destabilizing	0.999	D	0.795	deleterious	N	0.458748213	None	None	N
R/T	0.8687	likely_pathogenic	0.8562	pathogenic	-0.449	Destabilizing	0.999	D	0.769	deleterious	N	0.442184037	None	None	N
R/V	0.8314	likely_pathogenic	0.8171	pathogenic	0.09	Stabilizing	0.999	D	0.695	prob.delet.	None	None	None	None	N
R/W	0.6205	likely_pathogenic	0.6168	pathogenic	-0.011	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
R/Y	0.8215	likely_pathogenic	0.8163	pathogenic	0.289	Stabilizing	0.999	D	0.795	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.