TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7693	23302;23303;23304	chr2:178720942;178720941;178720940	chr2:179585669;179585668;179585667
N2AB	7376	22351;22352;22353	chr2:178720942;178720941;178720940	chr2:179585669;179585668;179585667
N2A	6449	19570;19571;19572	chr2:178720942;178720941;178720940	chr2:179585669;179585668;179585667
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-61
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.2776
• 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/G	None	None	0.738	N	0.579	0.416	0.414021929199	gnomAD-4.0.0	7.20196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87505E-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
S/A	0.1248	likely_benign	0.1647	benign	-0.587	Destabilizing	0.109	N	0.559	neutral	None	None	None	None	N
S/C	0.2914	likely_benign	0.3467	ambiguous	-0.329	Destabilizing	0.996	D	0.72	prob.delet.	D	0.532958565	None	None	N
S/D	0.7542	likely_pathogenic	0.9138	pathogenic	-0.279	Destabilizing	0.669	D	0.531	neutral	None	None	None	None	N
S/E	0.7799	likely_pathogenic	0.9182	pathogenic	-0.349	Destabilizing	0.849	D	0.544	neutral	None	None	None	None	N
S/F	0.3221	likely_benign	0.5319	ambiguous	-1.073	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
S/G	0.1728	likely_benign	0.2741	benign	-0.745	Destabilizing	0.738	D	0.579	neutral	N	0.520170227	None	None	N
S/H	0.5253	ambiguous	0.7516	pathogenic	-1.351	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
S/I	0.3475	ambiguous	0.5797	pathogenic	-0.287	Destabilizing	0.976	D	0.795	deleterious	N	0.504547961	None	None	N
S/K	0.8203	likely_pathogenic	0.9597	pathogenic	-0.629	Destabilizing	0.938	D	0.545	neutral	None	None	None	None	N
S/L	0.1614	likely_benign	0.2749	benign	-0.287	Destabilizing	0.938	D	0.743	deleterious	None	None	None	None	N
S/M	0.3453	ambiguous	0.5	ambiguous	0.175	Stabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
S/N	0.2997	likely_benign	0.5482	ambiguous	-0.41	Destabilizing	0.001	N	0.406	neutral	N	0.496292301	None	None	N
S/P	0.6682	likely_pathogenic	0.8925	pathogenic	-0.358	Destabilizing	0.989	D	0.734	prob.delet.	None	None	None	None	N
S/Q	0.6685	likely_pathogenic	0.8429	pathogenic	-0.718	Destabilizing	0.991	D	0.589	neutral	None	None	None	None	N
S/R	0.7208	likely_pathogenic	0.9223	pathogenic	-0.417	Destabilizing	0.976	D	0.727	prob.delet.	N	0.48377068	None	None	N
S/T	0.1208	likely_benign	0.1776	benign	-0.483	Destabilizing	0.002	N	0.26	neutral	N	0.506526304	None	None	N
S/V	0.3178	likely_benign	0.4976	ambiguous	-0.358	Destabilizing	0.849	D	0.753	deleterious	None	None	None	None	N
S/W	0.5627	ambiguous	0.7676	pathogenic	-1.032	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	N
S/Y	0.3304	likely_benign	0.5415	ambiguous	-0.769	Destabilizing	0.997	D	0.809	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.