TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33108	99547;99548;99549	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
N2AB	31467	94624;94625;94626	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
N2A	30540	91843;91844;91845	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
N2B	24043	72352;72353;72354	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
Novex-1	24168	72727;72728;72729	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
Novex-2	24235	72928;72929;72930	chr2:178537885;178537884;178537883	chr2:179402612;179402611;179402610
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-156
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3449
• 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/N	rs1281729370	0.043	0.081	N	0.232	0.136	0.0401082797425	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
K/N	rs1281729370	0.043	0.081	N	0.232	0.136	0.0401082797425	gnomAD-4.0.0	1.59466E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02792E-05

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	0.1653	likely_benign	0.2157	benign	0.035	Stabilizing	None	N	0.131	neutral	None	None	None	None	N
K/C	0.6271	likely_pathogenic	0.7251	pathogenic	-0.22	Destabilizing	0.757	D	0.249	neutral	None	None	None	None	N
K/D	0.2674	likely_benign	0.3442	ambiguous	-0.019	Destabilizing	0.055	N	0.333	neutral	None	None	None	None	N
K/E	0.0792	likely_benign	0.0859	benign	-0.024	Destabilizing	None	N	0.099	neutral	N	0.476648901	None	None	N
K/F	0.6539	likely_pathogenic	0.7399	pathogenic	-0.223	Destabilizing	0.139	N	0.281	neutral	None	None	None	None	N
K/G	0.2335	likely_benign	0.3201	benign	-0.141	Destabilizing	0.023	N	0.322	neutral	None	None	None	None	N
K/H	0.2438	likely_benign	0.3202	benign	-0.369	Destabilizing	0.145	N	0.29	neutral	None	None	None	None	N
K/I	0.2552	likely_benign	0.2929	benign	0.415	Stabilizing	0.002	N	0.359	neutral	None	None	None	None	N
K/L	0.2329	likely_benign	0.2843	benign	0.415	Stabilizing	None	N	0.339	neutral	None	None	None	None	N
K/M	0.1758	likely_benign	0.1999	benign	0.198	Stabilizing	None	N	0.248	neutral	N	0.492852942	None	None	N
K/N	0.1869	likely_benign	0.2358	benign	0.235	Stabilizing	0.081	N	0.232	neutral	N	0.519170314	None	None	N
K/P	0.5145	ambiguous	0.5779	pathogenic	0.315	Stabilizing	0.104	N	0.355	neutral	None	None	None	None	N
K/Q	0.0848	likely_benign	0.1018	benign	0.047	Stabilizing	None	N	0.123	neutral	N	0.459948652	None	None	N
K/R	0.088	likely_benign	0.0974	benign	-0.002	Destabilizing	0.008	N	0.28	neutral	N	0.484921668	None	None	N
K/S	0.1974	likely_benign	0.2664	benign	-0.225	Destabilizing	0.002	N	0.103	neutral	None	None	None	None	N
K/T	0.0985	likely_benign	0.1206	benign	-0.091	Destabilizing	0.005	N	0.323	neutral	N	0.51091619	None	None	N
K/V	0.2018	likely_benign	0.245	benign	0.315	Stabilizing	0.002	N	0.348	neutral	None	None	None	None	N
K/W	0.7241	likely_pathogenic	0.7937	pathogenic	-0.254	Destabilizing	0.934	D	0.26	neutral	None	None	None	None	N
K/Y	0.5497	ambiguous	0.64	pathogenic	0.105	Stabilizing	0.037	N	0.279	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.