TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31488	94687;94688;94689	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
N2AB	29847	89764;89765;89766	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
N2A	28920	86983;86984;86985	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
N2B	22423	67492;67493;67494	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
Novex-1	22548	67867;67868;67869	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
Novex-2	22615	68068;68069;68070	chr2:178547063;178547062;178547061	chr2:179411790;179411789;179411788
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: Fn3-117
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.6456
• Predicted PPI site: I

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/D	None	None	0.998	N	0.599	0.408	0.577403499239	gnomAD-4.0.0	1.59141E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85879E-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
A/C	0.4554	ambiguous	0.4455	ambiguous	-0.86	Destabilizing	1.0	D	0.281	neutral	None	None	None	None	I
A/D	0.4489	ambiguous	0.4353	ambiguous	-0.367	Destabilizing	0.998	D	0.599	neutral	N	0.461049438	None	None	I
A/E	0.3331	likely_benign	0.3338	benign	-0.506	Destabilizing	0.999	D	0.428	neutral	None	None	None	None	I
A/F	0.3355	likely_benign	0.3224	benign	-0.822	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	I
A/G	0.2242	likely_benign	0.1937	benign	-0.37	Destabilizing	0.993	D	0.297	neutral	N	0.517859939	None	None	I
A/H	0.5197	ambiguous	0.4994	ambiguous	-0.294	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	I
A/I	0.146	likely_benign	0.1492	benign	-0.334	Destabilizing	0.304	N	0.209	neutral	None	None	None	None	I
A/K	0.5487	ambiguous	0.548	ambiguous	-0.646	Destabilizing	0.999	D	0.426	neutral	None	None	None	None	I
A/L	0.1176	likely_benign	0.1216	benign	-0.334	Destabilizing	0.092	N	0.217	neutral	None	None	None	None	I
A/M	0.1312	likely_benign	0.1376	benign	-0.474	Destabilizing	0.991	D	0.433	neutral	None	None	None	None	I
A/N	0.2757	likely_benign	0.2512	benign	-0.393	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	I
A/P	0.5736	likely_pathogenic	0.4551	ambiguous	-0.291	Destabilizing	0.998	D	0.442	neutral	N	0.500685262	None	None	I
A/Q	0.3721	ambiguous	0.3614	ambiguous	-0.639	Destabilizing	0.999	D	0.427	neutral	None	None	None	None	I
A/R	0.5303	ambiguous	0.5241	ambiguous	-0.182	Destabilizing	0.999	D	0.441	neutral	None	None	None	None	I
A/S	0.1091	likely_benign	0.1018	benign	-0.63	Destabilizing	0.993	D	0.327	neutral	N	0.453238032	None	None	I
A/T	0.0831	likely_benign	0.0818	benign	-0.681	Destabilizing	0.98	D	0.311	neutral	N	0.502818703	None	None	I
A/V	0.0915	likely_benign	0.0896	benign	-0.291	Destabilizing	0.835	D	0.313	neutral	N	0.497932958	None	None	I
A/W	0.7829	likely_pathogenic	0.7553	pathogenic	-0.959	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
A/Y	0.4751	ambiguous	0.4542	ambiguous	-0.618	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	I

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.