TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8573	25942;25943;25944	chr2:178715697;178715696;178715695	chr2:179580424;179580423;179580422
N2AB	8256	24991;24992;24993	chr2:178715697;178715696;178715695	chr2:179580424;179580423;179580422
N2A	7329	22210;22211;22212	chr2:178715697;178715696;178715695	chr2:179580424;179580423;179580422
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-71
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1214
• 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
I/L	rs142609645	-0.557	0.009	N	0.453	0.236	None	gnomAD-2.1.1	1.1E-05	None	None	None	None	N	None	1.27378E-04	0	None	0	0	None	0	None	0	0	0
I/L	rs142609645	-0.557	0.009	N	0.453	0.236	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	2.65393E-04	0	0	0	0	None	0	0	0	0	0
I/L	rs142609645	-0.557	0.009	N	0.453	0.236	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/L	rs142609645	-0.557	0.009	N	0.453	0.236	None	gnomAD-4.0.0	8.07615E-06	None	None	None	None	N	None	1.73356E-04	0	None	0	0	None	0	0	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
I/A	0.6483	likely_pathogenic	0.6129	pathogenic	-2.351	Highly Destabilizing	0.025	N	0.441	neutral	None	None	None	None	N
I/C	0.9691	likely_pathogenic	0.9637	pathogenic	-1.388	Destabilizing	0.992	D	0.771	deleterious	None	None	None	None	N
I/D	0.9976	likely_pathogenic	0.9973	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/E	0.9927	likely_pathogenic	0.9912	pathogenic	-2.147	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
I/F	0.5792	likely_pathogenic	0.5548	ambiguous	-1.313	Destabilizing	0.827	D	0.751	deleterious	N	0.494347426	None	None	N
I/G	0.9737	likely_pathogenic	0.9678	pathogenic	-2.95	Highly Destabilizing	0.82	D	0.779	deleterious	None	None	None	None	N
I/H	0.9943	likely_pathogenic	0.993	pathogenic	-2.476	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
I/K	0.9904	likely_pathogenic	0.989	pathogenic	-1.556	Destabilizing	0.967	D	0.811	deleterious	None	None	None	None	N
I/L	0.2224	likely_benign	0.2009	benign	-0.588	Destabilizing	0.009	N	0.453	neutral	N	0.491269553	None	None	N
I/M	0.2258	likely_benign	0.2287	benign	-0.574	Destabilizing	0.785	D	0.691	prob.neutral	D	0.52982192	None	None	N
I/N	0.9746	likely_pathogenic	0.9714	pathogenic	-2.06	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.541685205	None	None	N
I/P	0.9885	likely_pathogenic	0.9856	pathogenic	-1.16	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/Q	0.9895	likely_pathogenic	0.9875	pathogenic	-1.776	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
I/R	0.9835	likely_pathogenic	0.9803	pathogenic	-1.566	Destabilizing	0.997	D	0.829	deleterious	None	None	None	None	N
I/S	0.8992	likely_pathogenic	0.884	pathogenic	-2.776	Highly Destabilizing	0.981	D	0.75	deleterious	N	0.499298176	None	None	N
I/T	0.4917	ambiguous	0.4528	ambiguous	-2.322	Highly Destabilizing	0.97	D	0.706	prob.neutral	N	0.493333468	None	None	N
I/V	0.0933	likely_benign	0.0769	benign	-1.16	Destabilizing	None	N	0.216	neutral	N	0.407932603	None	None	N
I/W	0.9879	likely_pathogenic	0.9877	pathogenic	-1.693	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
I/Y	0.9644	likely_pathogenic	0.9616	pathogenic	-1.381	Destabilizing	0.979	D	0.789	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.