TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33709	101350;101351;101352	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
N2AB	32068	96427;96428;96429	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
N2A	31141	93646;93647;93648	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
N2B	24644	74155;74156;74157	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
Novex-1	24769	74530;74531;74532	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
Novex-2	24836	74731;74732;74733	chr2:178535490;178535489;178535488	chr2:179400217;179400216;179400215
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-132
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3231
• 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
T/I	None	None	0.995	N	0.551	0.293	0.377274123778	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79888E-06	0	0
T/K	None	None	0.965	N	0.407	0.237	0.284539287134	gnomAD-4.0.0	6.84201E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99442E-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
T/A	0.141	likely_benign	0.1328	benign	-0.904	Destabilizing	0.286	N	0.427	neutral	N	0.470092996	None	None	N
T/C	0.4588	ambiguous	0.4605	ambiguous	-0.52	Destabilizing	1.0	D	0.588	neutral	None	None	None	None	N
T/D	0.5529	ambiguous	0.5593	ambiguous	-0.61	Destabilizing	0.799	D	0.424	neutral	None	None	None	None	N
T/E	0.3925	ambiguous	0.3941	ambiguous	-0.481	Destabilizing	0.262	N	0.369	neutral	None	None	None	None	N
T/F	0.252	likely_benign	0.237	benign	-0.671	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
T/G	0.4399	ambiguous	0.4339	ambiguous	-1.276	Destabilizing	0.985	D	0.492	neutral	None	None	None	None	N
T/H	0.2637	likely_benign	0.2724	benign	-1.486	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
T/I	0.1623	likely_benign	0.1446	benign	0.04	Stabilizing	0.995	D	0.551	neutral	N	0.468890477	None	None	N
T/K	0.3224	likely_benign	0.3154	benign	-0.469	Destabilizing	0.965	D	0.407	neutral	N	0.444695906	None	None	N
T/L	0.1286	likely_benign	0.1179	benign	0.04	Stabilizing	0.987	D	0.438	neutral	None	None	None	None	N
T/M	0.1121	likely_benign	0.107	benign	0.056	Stabilizing	1.0	D	0.573	neutral	None	None	None	None	N
T/N	0.1657	likely_benign	0.1646	benign	-0.838	Destabilizing	0.096	N	0.235	neutral	None	None	None	None	N
T/P	0.8311	likely_pathogenic	0.7838	pathogenic	-0.242	Destabilizing	0.977	D	0.542	neutral	N	0.495388523	None	None	N
T/Q	0.267	likely_benign	0.2693	benign	-0.736	Destabilizing	0.984	D	0.519	neutral	None	None	None	None	N
T/R	0.2705	likely_benign	0.2482	benign	-0.564	Destabilizing	0.996	D	0.521	neutral	N	0.472189152	None	None	N
T/S	0.1342	likely_benign	0.134	benign	-1.108	Destabilizing	0.07	N	0.405	neutral	N	0.387490255	None	None	N
T/V	0.1549	likely_benign	0.1458	benign	-0.242	Destabilizing	0.982	D	0.389	neutral	None	None	None	None	N
T/W	0.6496	likely_pathogenic	0.6434	pathogenic	-0.744	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/Y	0.3376	likely_benign	0.3217	benign	-0.403	Destabilizing	1.0	D	0.648	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.