TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2534	7825;7826;7827	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
N2AB	2534	7825;7826;7827	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
N2A	2534	7825;7826;7827	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
N2B	2488	7687;7688;7689	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
Novex-1	2488	7687;7688;7689	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
Novex-2	2488	7687;7688;7689	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089
Novex-3	2534	7825;7826;7827	chr2:178773364;178773363;178773362	chr2:179638091;179638090;179638089

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-15
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6947
• 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
K/E	rs767167863	0.292	0.012	N	0.153	0.321	0.224531998449	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	1.77E-05	0
K/E	rs767167863	0.292	0.012	N	0.153	0.321	0.224531998449	gnomAD-4.0.0	6.36343E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	None	0	0	8.57016E-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
K/A	0.2543	likely_benign	0.2826	benign	-0.128	Destabilizing	0.525	D	0.315	neutral	None	None	None	None	N
K/C	0.5872	likely_pathogenic	0.624	pathogenic	-0.29	Destabilizing	0.998	D	0.241	neutral	None	None	None	None	N
K/D	0.2989	likely_benign	0.3147	benign	0.035	Stabilizing	0.728	D	0.321	neutral	None	None	None	None	N
K/E	0.0996	likely_benign	0.1093	benign	0.103	Stabilizing	0.012	N	0.153	neutral	N	0.442882001	None	None	N
K/F	0.7111	likely_pathogenic	0.7214	pathogenic	-0.02	Destabilizing	0.974	D	0.283	neutral	None	None	None	None	N
K/G	0.3729	ambiguous	0.4099	ambiguous	-0.408	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
K/H	0.189	likely_benign	0.2115	benign	-0.584	Destabilizing	0.016	N	0.205	neutral	None	None	None	None	N
K/I	0.3401	ambiguous	0.3528	ambiguous	0.561	Stabilizing	0.966	D	0.305	neutral	D	0.563749989	None	None	N
K/L	0.3463	ambiguous	0.367	ambiguous	0.561	Stabilizing	0.842	D	0.319	neutral	None	None	None	None	N
K/M	0.2269	likely_benign	0.2401	benign	0.137	Stabilizing	0.991	D	0.259	neutral	None	None	None	None	N
K/N	0.194	likely_benign	0.2055	benign	-0.042	Destabilizing	0.801	D	0.232	neutral	D	0.56216408	None	None	N
K/P	0.7381	likely_pathogenic	0.7833	pathogenic	0.361	Stabilizing	0.974	D	0.344	neutral	None	None	None	None	N
K/Q	0.0921	likely_benign	0.106	benign	-0.087	Destabilizing	0.136	N	0.211	neutral	N	0.496956759	None	None	N
K/R	0.0855	likely_benign	0.0934	benign	-0.213	Destabilizing	0.801	D	0.266	neutral	N	0.511698882	None	None	N
K/S	0.2274	likely_benign	0.2459	benign	-0.525	Destabilizing	0.172	N	0.161	neutral	None	None	None	None	N
K/T	0.1083	likely_benign	0.121	benign	-0.281	Destabilizing	0.669	D	0.324	neutral	N	0.511804886	None	None	N
K/V	0.2893	likely_benign	0.3162	benign	0.361	Stabilizing	0.915	D	0.328	neutral	None	None	None	None	N
K/W	0.7072	likely_pathogenic	0.7318	pathogenic	-0.033	Destabilizing	0.998	D	0.289	neutral	None	None	None	None	N
K/Y	0.5374	ambiguous	0.5561	ambiguous	0.276	Stabilizing	0.949	D	0.309	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.