TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33398	100417;100418;100419	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
N2AB	31757	95494;95495;95496	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
N2A	30830	92713;92714;92715	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
N2B	24333	73222;73223;73224	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
Novex-1	24458	73597;73598;73599	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
Novex-2	24525	73798;73799;73800	chr2:178536555;178536554;178536553	chr2:179401282;179401281;179401280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-131
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5289
• 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/Q	None	None	0.012	N	0.114	0.065	0.104622674875	gnomAD-4.0.0	1.94455E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.04591E-05	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	0.3438	ambiguous	0.2729	benign	-0.299	Destabilizing	0.543	D	0.418	neutral	None	None	None	None	N
K/C	0.6257	likely_pathogenic	0.507	ambiguous	-0.333	Destabilizing	0.996	D	0.524	neutral	None	None	None	None	N
K/D	0.7069	likely_pathogenic	0.6912	pathogenic	-0.014	Destabilizing	0.742	D	0.421	neutral	None	None	None	None	N
K/E	0.2147	likely_benign	0.196	benign	0.02	Stabilizing	0.309	N	0.489	neutral	N	0.496911451	None	None	N
K/F	0.6855	likely_pathogenic	0.6135	pathogenic	-0.338	Destabilizing	0.984	D	0.468	neutral	None	None	None	None	N
K/G	0.5769	likely_pathogenic	0.513	ambiguous	-0.572	Destabilizing	0.742	D	0.425	neutral	None	None	None	None	N
K/H	0.3741	ambiguous	0.2998	benign	-0.954	Destabilizing	0.953	D	0.446	neutral	None	None	None	None	N
K/I	0.2178	likely_benign	0.1914	benign	0.365	Stabilizing	0.939	D	0.473	neutral	N	0.48225143	None	None	N
K/L	0.296	likely_benign	0.2389	benign	0.365	Stabilizing	0.742	D	0.425	neutral	None	None	None	None	N
K/M	0.181	likely_benign	0.1634	benign	0.373	Stabilizing	0.953	D	0.445	neutral	None	None	None	None	N
K/N	0.3897	ambiguous	0.3635	ambiguous	-0.016	Destabilizing	0.684	D	0.419	neutral	N	0.458310203	None	None	N
K/P	0.5109	ambiguous	0.3811	ambiguous	0.174	Stabilizing	0.953	D	0.455	neutral	None	None	None	None	N
K/Q	0.1269	likely_benign	0.1	benign	-0.253	Destabilizing	0.012	N	0.114	neutral	N	0.437652504	None	None	N
K/R	0.1071	likely_benign	0.1003	benign	-0.271	Destabilizing	0.007	N	0.248	neutral	N	0.462876235	None	None	N
K/S	0.4278	ambiguous	0.3741	ambiguous	-0.636	Destabilizing	0.742	D	0.403	neutral	None	None	None	None	N
K/T	0.179	likely_benign	0.1566	benign	-0.43	Destabilizing	0.684	D	0.418	neutral	N	0.429187736	None	None	N
K/V	0.2648	likely_benign	0.2231	benign	0.174	Stabilizing	0.953	D	0.427	neutral	None	None	None	None	N
K/W	0.8415	likely_pathogenic	0.779	pathogenic	-0.222	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
K/Y	0.5743	likely_pathogenic	0.5203	ambiguous	0.103	Stabilizing	0.984	D	0.469	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.