TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21450	64573;64574;64575	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
N2AB	19809	59650;59651;59652	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
N2A	18882	56869;56870;56871	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
N2B	12385	37378;37379;37380	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
Novex-1	12510	37753;37754;37755	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
Novex-2	12577	37954;37955;37956	chr2:178586553;178586552;178586551	chr2:179451280;179451279;179451278
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: Fn3-43
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.0735
• 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/R	None	None	0.991	N	0.759	0.459	0.371718192555	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
S/T	None	None	0.969	D	0.711	0.396	0.335910606209	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	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	0.6347	likely_pathogenic	0.611	pathogenic	-0.707	Destabilizing	0.807	D	0.689	prob.neutral	None	None	None	None	N
S/C	0.869	likely_pathogenic	0.8392	pathogenic	-0.66	Destabilizing	0.999	D	0.721	prob.delet.	N	0.520645575	None	None	N
S/D	0.9937	likely_pathogenic	0.9915	pathogenic	-1.155	Destabilizing	0.976	D	0.745	deleterious	None	None	None	None	N
S/E	0.9978	likely_pathogenic	0.9971	pathogenic	-1.075	Destabilizing	0.976	D	0.757	deleterious	None	None	None	None	N
S/F	0.9973	likely_pathogenic	0.9962	pathogenic	-0.549	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
S/G	0.137	likely_benign	0.1466	benign	-1.032	Destabilizing	0.02	N	0.46	neutral	N	0.432600895	None	None	N
S/H	0.9945	likely_pathogenic	0.9927	pathogenic	-1.484	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
S/I	0.9972	likely_pathogenic	0.9957	pathogenic	0.077	Stabilizing	0.997	D	0.768	deleterious	N	0.520392085	None	None	N
S/K	0.9995	likely_pathogenic	0.9994	pathogenic	-0.887	Destabilizing	0.976	D	0.757	deleterious	None	None	None	None	N
S/L	0.9876	likely_pathogenic	0.9837	pathogenic	0.077	Stabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
S/M	0.9933	likely_pathogenic	0.9912	pathogenic	0.164	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
S/N	0.9806	likely_pathogenic	0.9755	pathogenic	-1.134	Destabilizing	0.939	D	0.727	prob.delet.	D	0.531152506	None	None	N
S/P	0.9967	likely_pathogenic	0.9958	pathogenic	-0.149	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
S/Q	0.9965	likely_pathogenic	0.9956	pathogenic	-1.13	Destabilizing	0.998	D	0.752	deleterious	None	None	None	None	N
S/R	0.9988	likely_pathogenic	0.9986	pathogenic	-0.922	Destabilizing	0.991	D	0.759	deleterious	N	0.519885106	None	None	N
S/T	0.905	likely_pathogenic	0.8817	pathogenic	-0.942	Destabilizing	0.969	D	0.711	prob.delet.	D	0.530138548	None	None	N
S/V	0.9959	likely_pathogenic	0.9941	pathogenic	-0.149	Destabilizing	0.993	D	0.768	deleterious	None	None	None	None	N
S/W	0.9979	likely_pathogenic	0.997	pathogenic	-0.684	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
S/Y	0.9957	likely_pathogenic	0.994	pathogenic	-0.359	Destabilizing	0.998	D	0.773	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.