TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4651	14176;14177;14178	chr2:178739282;178739281;178739280	chr2:179604009;179604008;179604007
N2AB	4334	13225;13226;13227	chr2:178739282;178739281;178739280	chr2:179604009;179604008;179604007
N2A	None	None	chr2:None	chr2:None
N2B	4288	13087;13088;13089	chr2:178739282;178739281;178739280	chr2:179604009;179604008;179604007
Novex-1	4413	13462;13463;13464	chr2:178739282;178739281;178739280	chr2:179604009;179604008;179604007
Novex-2	4480	13663;13664;13665	chr2:178739282;178739281;178739280	chr2:179604009;179604008;179604007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-29
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.4192
• 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	rs1244637034	0.161	0.454	N	0.332	0.198	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/E	rs1244637034	0.161	0.454	N	0.332	0.198	None	gnomAD-4.0.0	3.18786E-06	None	None	None	None	N	None	0	2.28843E-05	None	0	0	None	0	0	0	1.4339E-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	0.3444	ambiguous	0.4017	ambiguous	-0.588	Destabilizing	0.688	D	0.311	neutral	None	None	None	None	N
K/C	0.6373	likely_pathogenic	0.6767	pathogenic	-0.697	Destabilizing	0.998	D	0.416	neutral	None	None	None	None	N
K/D	0.5365	ambiguous	0.6095	pathogenic	-0.586	Destabilizing	0.842	D	0.333	neutral	None	None	None	None	N
K/E	0.1581	likely_benign	0.1859	benign	-0.47	Destabilizing	0.454	N	0.332	neutral	N	0.512650861	None	None	N
K/F	0.6624	likely_pathogenic	0.7197	pathogenic	-0.347	Destabilizing	0.949	D	0.418	neutral	None	None	None	None	N
K/G	0.4979	ambiguous	0.5942	pathogenic	-0.97	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
K/H	0.2304	likely_benign	0.2445	benign	-1.454	Destabilizing	0.974	D	0.371	neutral	None	None	None	None	N
K/I	0.2598	likely_benign	0.291	benign	0.408	Stabilizing	0.904	D	0.381	neutral	None	None	None	None	N
K/L	0.2816	likely_benign	0.3235	benign	0.408	Stabilizing	0.275	N	0.343	neutral	None	None	None	None	N
K/M	0.2175	likely_benign	0.2396	benign	0.405	Stabilizing	0.267	N	0.302	neutral	N	0.516557071	None	None	N
K/N	0.3392	likely_benign	0.4077	ambiguous	-0.715	Destabilizing	0.801	D	0.322	neutral	D	0.55264375	None	None	N
K/P	0.8774	likely_pathogenic	0.9246	pathogenic	0.107	Stabilizing	0.974	D	0.358	neutral	None	None	None	None	N
K/Q	0.1121	likely_benign	0.1185	benign	-0.799	Destabilizing	0.051	N	0.196	neutral	N	0.498946445	None	None	N
K/R	0.0867	likely_benign	0.0889	benign	-0.804	Destabilizing	0.005	N	0.081	neutral	N	0.501573347	None	None	N
K/S	0.3262	likely_benign	0.3888	ambiguous	-1.311	Destabilizing	0.842	D	0.291	neutral	None	None	None	None	N
K/T	0.1468	likely_benign	0.1605	benign	-0.985	Destabilizing	0.801	D	0.315	neutral	N	0.515823936	None	None	N
K/V	0.2844	likely_benign	0.3111	benign	0.107	Stabilizing	0.728	D	0.357	neutral	None	None	None	None	N
K/W	0.6992	likely_pathogenic	0.7408	pathogenic	-0.271	Destabilizing	0.998	D	0.447	neutral	None	None	None	None	N
K/Y	0.5242	ambiguous	0.5713	pathogenic	0.07	Stabilizing	0.974	D	0.407	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.