TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14213	42862;42863;42864	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
N2AB	12572	37939;37940;37941	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
N2A	11645	35158;35159;35160	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
N2B	5148	15667;15668;15669	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
Novex-1	5273	16042;16043;16044	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
Novex-2	5340	16243;16244;16245	chr2:178633862;178633861;178633860	chr2:179498589;179498588;179498587
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-92
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0771
• 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
A/S	None	None	0.581	D	0.675	0.322	0.208816687407	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	0	0	None	0	2.5208E-05	None	0	0	8.99611E-07	0	0
A/T	rs892930093	None	0.41	D	0.749	0.334	0.212008924253	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	0	0	None	0	2.5208E-05	None	0	0	8.99611E-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
A/C	0.5826	likely_pathogenic	0.6046	pathogenic	-0.764	Destabilizing	0.98	D	0.791	deleterious	None	None	None	None	N
A/D	0.9963	likely_pathogenic	0.9955	pathogenic	-2.152	Highly Destabilizing	0.908	D	0.909	deleterious	D	0.535363411	None	None	N
A/E	0.9913	likely_pathogenic	0.9894	pathogenic	-1.89	Destabilizing	0.929	D	0.863	deleterious	None	None	None	None	N
A/F	0.7967	likely_pathogenic	0.7936	pathogenic	-0.493	Destabilizing	0.866	D	0.915	deleterious	None	None	None	None	N
A/G	0.3147	likely_benign	0.3476	ambiguous	-1.502	Destabilizing	0.738	D	0.657	neutral	D	0.535363411	None	None	N
A/H	0.9945	likely_pathogenic	0.993	pathogenic	-2.037	Highly Destabilizing	0.993	D	0.898	deleterious	None	None	None	None	N
A/I	0.6252	likely_pathogenic	0.5022	ambiguous	0.531	Stabilizing	0.241	N	0.809	deleterious	None	None	None	None	N
A/K	0.9979	likely_pathogenic	0.9971	pathogenic	-0.888	Destabilizing	0.929	D	0.865	deleterious	None	None	None	None	N
A/L	0.4408	ambiguous	0.4199	ambiguous	0.531	Stabilizing	0.48	N	0.756	deleterious	None	None	None	None	N
A/M	0.6319	likely_pathogenic	0.5802	pathogenic	0.238	Stabilizing	0.961	D	0.868	deleterious	None	None	None	None	N
A/N	0.9835	likely_pathogenic	0.9808	pathogenic	-1.332	Destabilizing	0.976	D	0.906	deleterious	None	None	None	None	N
A/P	0.9943	likely_pathogenic	0.9909	pathogenic	0.077	Stabilizing	0.968	D	0.874	deleterious	D	0.535363411	None	None	N
A/Q	0.9853	likely_pathogenic	0.9828	pathogenic	-1.009	Destabilizing	0.976	D	0.871	deleterious	None	None	None	None	N
A/R	0.9929	likely_pathogenic	0.991	pathogenic	-1.209	Destabilizing	0.929	D	0.869	deleterious	None	None	None	None	N
A/S	0.5465	ambiguous	0.4775	ambiguous	-1.754	Destabilizing	0.581	D	0.675	neutral	D	0.535363411	None	None	N
A/T	0.5745	likely_pathogenic	0.4284	ambiguous	-1.349	Destabilizing	0.41	N	0.749	deleterious	D	0.533787849	None	None	N
A/V	0.2933	likely_benign	0.1904	benign	0.077	Stabilizing	0.01	N	0.417	neutral	N	0.436280857	None	None	N
A/W	0.9939	likely_pathogenic	0.9934	pathogenic	-1.359	Destabilizing	0.993	D	0.895	deleterious	None	None	None	None	N
A/Y	0.9581	likely_pathogenic	0.9596	pathogenic	-0.742	Destabilizing	0.929	D	0.916	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.