TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4642	14149;14150;14151	chr2:178739309;178739308;178739307	chr2:179604036;179604035;179604034
N2AB	4325	13198;13199;13200	chr2:178739309;178739308;178739307	chr2:179604036;179604035;179604034
N2A	None	None	chr2:None	chr2:None
N2B	4279	13060;13061;13062	chr2:178739309;178739308;178739307	chr2:179604036;179604035;179604034
Novex-1	4404	13435;13436;13437	chr2:178739309;178739308;178739307	chr2:179604036;179604035;179604034
Novex-2	4471	13636;13637;13638	chr2:178739309;178739308;178739307	chr2:179604036;179604035;179604034
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: Ig-29
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.6849
• 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	rs371961804	0.449	None	N	0.199	0.077	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	1.29199E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs371961804	0.449	None	N	0.199	0.077	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.23E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs371961804	0.449	None	N	0.199	0.077	None	gnomAD-4.0.0	1.97099E-05	None	None	None	None	N	None	7.23484E-05	0	None	0	0	None	0	0	0	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	0.2436	likely_benign	0.2374	benign	-0.099	Destabilizing	0.016	N	0.322	neutral	None	None	None	None	N
K/C	0.5145	ambiguous	0.5152	ambiguous	-0.356	Destabilizing	0.864	D	0.245	neutral	None	None	None	None	N
K/D	0.3465	ambiguous	0.3629	ambiguous	-0.03	Destabilizing	None	N	0.247	neutral	None	None	None	None	N
K/E	0.1181	likely_benign	0.1219	benign	0.03	Stabilizing	None	N	0.199	neutral	N	0.499831619	None	None	N
K/F	0.5814	likely_pathogenic	0.5894	pathogenic	-0.057	Destabilizing	0.628	D	0.275	neutral	None	None	None	None	N
K/G	0.3178	likely_benign	0.3496	ambiguous	-0.369	Destabilizing	0.016	N	0.323	neutral	None	None	None	None	N
K/H	0.206	likely_benign	0.2019	benign	-0.589	Destabilizing	0.214	N	0.282	neutral	None	None	None	None	N
K/I	0.2161	likely_benign	0.2067	benign	0.556	Stabilizing	0.295	N	0.301	neutral	N	0.51141481	None	None	N
K/L	0.2539	likely_benign	0.259	benign	0.556	Stabilizing	0.072	N	0.367	neutral	None	None	None	None	N
K/M	0.1588	likely_benign	0.1533	benign	0.134	Stabilizing	0.628	D	0.281	neutral	None	None	None	None	N
K/N	0.207	likely_benign	0.2066	benign	-0.118	Destabilizing	None	N	0.241	neutral	N	0.512741741	None	None	N
K/P	0.8578	likely_pathogenic	0.8985	pathogenic	0.368	Stabilizing	0.136	N	0.347	neutral	None	None	None	None	N
K/Q	0.0963	likely_benign	0.0942	benign	-0.17	Destabilizing	0.002	N	0.199	neutral	N	0.494365855	None	None	N
K/R	0.0829	likely_benign	0.0835	benign	-0.261	Destabilizing	None	N	0.195	neutral	N	0.514669587	None	None	N
K/S	0.2412	likely_benign	0.2427	benign	-0.576	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	N
K/T	0.1094	likely_benign	0.0989	benign	-0.344	Destabilizing	0.029	N	0.341	neutral	N	0.515160847	None	None	N
K/V	0.2145	likely_benign	0.2038	benign	0.368	Stabilizing	0.072	N	0.383	neutral	None	None	None	None	N
K/W	0.6576	likely_pathogenic	0.6811	pathogenic	-0.083	Destabilizing	0.864	D	0.263	neutral	None	None	None	None	N
K/Y	0.443	ambiguous	0.4507	ambiguous	0.24	Stabilizing	0.628	D	0.28	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.