TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35165	105718;105719;105720	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
N2AB	33524	100795;100796;100797	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
N2A	32597	98014;98015;98016	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
N2B	26100	78523;78524;78525	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
Novex-1	26225	78898;78899;78900	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
Novex-2	26292	79099;79100;79101	chr2:178531122;178531121;178531120	chr2:179395849;179395848;179395847
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-164
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.7974
• 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	rs879156291	None	None	N	0.113	0.073	None	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/E	rs879156291	None	None	N	0.113	0.073	None	gnomAD-4.0.0	2.02984E-06	None	None	None	None	N	None	3.49504E-05	0	None	0	0	None	0	0	0	0	0
K/T	None	None	None	N	0.233	0.043	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.1275	likely_benign	0.1215	benign	0.097	Stabilizing	None	N	0.191	neutral	None	None	None	None	N
K/C	0.4179	ambiguous	0.4051	ambiguous	-0.238	Destabilizing	0.017	N	0.462	neutral	None	None	None	None	N
K/D	0.15	likely_benign	0.1364	benign	-0.005	Destabilizing	None	N	0.224	neutral	None	None	None	None	N
K/E	0.0854	likely_benign	0.0839	benign	-0.005	Destabilizing	None	N	0.113	neutral	N	0.394485224	None	None	N
K/F	0.6184	likely_pathogenic	0.6041	pathogenic	-0.152	Destabilizing	0.003	N	0.462	neutral	None	None	None	None	N
K/G	0.0662	likely_benign	0.0638	benign	-0.079	Destabilizing	None	N	0.195	neutral	None	None	None	None	N
K/H	0.2023	likely_benign	0.1832	benign	-0.29	Destabilizing	None	N	0.18	neutral	None	None	None	None	N
K/I	0.3535	ambiguous	0.3289	benign	0.478	Stabilizing	None	N	0.432	neutral	N	0.457996292	None	None	N
K/L	0.2485	likely_benign	0.2534	benign	0.478	Stabilizing	None	N	0.236	neutral	None	None	None	None	N
K/M	0.1955	likely_benign	0.2022	benign	0.172	Stabilizing	0.017	N	0.448	neutral	None	None	None	None	N
K/N	0.1101	likely_benign	0.1057	benign	0.232	Stabilizing	None	N	0.167	neutral	N	0.373355017	None	None	N
K/P	0.4842	ambiguous	0.4832	ambiguous	0.378	Stabilizing	0.001	N	0.311	neutral	None	None	None	None	N
K/Q	0.0926	likely_benign	0.0856	benign	0.072	Stabilizing	None	N	0.191	neutral	N	0.443105891	None	None	N
K/R	0.0813	likely_benign	0.0748	benign	0.004	Stabilizing	None	N	0.117	neutral	N	0.448762427	None	None	N
K/S	0.1207	likely_benign	0.1117	benign	-0.205	Destabilizing	None	N	0.153	neutral	None	None	None	None	N
K/T	0.1276	likely_benign	0.1246	benign	-0.067	Destabilizing	None	N	0.233	neutral	N	0.487723459	None	None	N
K/V	0.2873	likely_benign	0.2656	benign	0.378	Stabilizing	None	N	0.231	neutral	None	None	None	None	N
K/W	0.5345	ambiguous	0.5055	ambiguous	-0.208	Destabilizing	0.152	N	0.411	neutral	None	None	None	None	N
K/Y	0.398	ambiguous	0.3697	ambiguous	0.156	Stabilizing	0.001	N	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.