TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33105	99538;99539;99540	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
N2AB	31464	94615;94616;94617	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
N2A	30537	91834;91835;91836	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
N2B	24040	72343;72344;72345	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
Novex-1	24165	72718;72719;72720	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
Novex-2	24232	72919;72920;72921	chr2:178537894;178537893;178537892	chr2:179402621;179402620;179402619
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-156
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.169
• 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/I	rs1196579817	0.703	0.185	N	0.381	0.275	0.578164481777	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
K/I	rs1196579817	0.703	0.185	N	0.381	0.275	0.578164481777	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/I	rs1196579817	0.703	0.185	N	0.381	0.275	0.578164481777	gnomAD-4.0.0	2.56885E-06	None	None	None	None	N	None	1.69296E-05	0	None	0	0	None	0	0	2.40021E-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	0.2803	likely_benign	0.3116	benign	-0.212	Destabilizing	0.019	N	0.153	neutral	None	None	None	None	N
K/C	0.7147	likely_pathogenic	0.7459	pathogenic	-0.274	Destabilizing	0.992	D	0.359	neutral	None	None	None	None	N
K/D	0.4993	ambiguous	0.4835	ambiguous	-0.111	Destabilizing	0.418	N	0.273	neutral	None	None	None	None	N
K/E	0.1174	likely_benign	0.1058	benign	-0.053	Destabilizing	0.002	N	0.105	neutral	N	0.434068773	None	None	N
K/F	0.7679	likely_pathogenic	0.7929	pathogenic	-0.03	Destabilizing	0.925	D	0.361	neutral	None	None	None	None	N
K/G	0.3994	ambiguous	0.4439	ambiguous	-0.522	Destabilizing	0.589	D	0.311	neutral	None	None	None	None	N
K/H	0.2975	likely_benign	0.3437	ambiguous	-0.853	Destabilizing	0.676	D	0.337	neutral	None	None	None	None	N
K/I	0.3405	ambiguous	0.3389	benign	0.562	Stabilizing	0.185	N	0.381	neutral	N	0.498253537	None	None	N
K/L	0.3045	likely_benign	0.3351	benign	0.562	Stabilizing	0.04	N	0.317	neutral	None	None	None	None	N
K/M	0.2067	likely_benign	0.2094	benign	0.371	Stabilizing	0.549	D	0.339	neutral	None	None	None	None	N
K/N	0.3338	likely_benign	0.3216	benign	-0.12	Destabilizing	0.52	D	0.251	neutral	N	0.500389765	None	None	N
K/P	0.8854	likely_pathogenic	0.8793	pathogenic	0.335	Stabilizing	0.911	D	0.331	neutral	None	None	None	None	N
K/Q	0.0854	likely_benign	0.1027	benign	-0.256	Destabilizing	0.002	N	0.104	neutral	N	0.462079306	None	None	N
K/R	0.0904	likely_benign	0.0999	benign	-0.42	Destabilizing	0.091	N	0.215	neutral	N	0.49584795	None	None	N
K/S	0.3172	likely_benign	0.3474	ambiguous	-0.652	Destabilizing	0.229	N	0.223	neutral	None	None	None	None	N
K/T	0.1289	likely_benign	0.1379	benign	-0.418	Destabilizing	0.245	N	0.266	neutral	N	0.497752105	None	None	N
K/V	0.2724	likely_benign	0.2913	benign	0.335	Stabilizing	0.053	N	0.315	neutral	None	None	None	None	N
K/W	0.7695	likely_pathogenic	0.808	pathogenic	0.044	Stabilizing	0.994	D	0.399	neutral	None	None	None	None	N
K/Y	0.6595	likely_pathogenic	0.6709	pathogenic	0.328	Stabilizing	0.322	N	0.365	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.