TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14202	42829;42830;42831	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
N2AB	12561	37906;37907;37908	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
N2A	11634	35125;35126;35127	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
N2B	5137	15634;15635;15636	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
Novex-1	5262	16009;16010;16011	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
Novex-2	5329	16210;16211;16212	chr2:178633895;178633894;178633893	chr2:179498622;179498621;179498620
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-92
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.6917
• 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
E/G	rs765485610	-0.346	0.978	N	0.52	0.4	0.282575091529	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/G	rs765485610	-0.346	0.978	N	0.52	0.4	0.282575091529	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
E/G	rs765485610	-0.346	0.978	N	0.52	0.4	0.282575091529	gnomAD-4.0.0	5.1265E-06	None	None	None	None	N	None	6.76796E-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
E/A	0.2319	likely_benign	0.2738	benign	-0.346	Destabilizing	0.989	D	0.569	neutral	N	0.449583316	None	None	N
E/C	0.9222	likely_pathogenic	0.9514	pathogenic	0.147	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.15	likely_benign	0.1525	benign	-0.189	Destabilizing	0.054	N	0.224	neutral	N	0.428029729	None	None	N
E/F	0.8294	likely_pathogenic	0.9024	pathogenic	-0.321	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/G	0.2004	likely_benign	0.2584	benign	-0.513	Destabilizing	0.978	D	0.52	neutral	N	0.449076524	None	None	N
E/H	0.6548	likely_pathogenic	0.7786	pathogenic	-0.149	Destabilizing	1.0	D	0.567	neutral	None	None	None	None	N
E/I	0.6553	likely_pathogenic	0.7412	pathogenic	0.052	Stabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.3227	likely_benign	0.4737	ambiguous	0.589	Stabilizing	0.978	D	0.537	neutral	N	0.44496788	None	None	N
E/L	0.6647	likely_pathogenic	0.7399	pathogenic	0.052	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/M	0.6264	likely_pathogenic	0.7064	pathogenic	0.201	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/N	0.2788	likely_benign	0.3466	ambiguous	0.264	Stabilizing	0.995	D	0.567	neutral	None	None	None	None	N
E/P	0.91	likely_pathogenic	0.9509	pathogenic	-0.061	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/Q	0.2615	likely_benign	0.3341	benign	0.287	Stabilizing	0.997	D	0.56	neutral	N	0.452431534	None	None	N
E/R	0.4641	ambiguous	0.6338	pathogenic	0.639	Stabilizing	0.998	D	0.593	neutral	None	None	None	None	N
E/S	0.3111	likely_benign	0.3747	ambiguous	0.136	Stabilizing	0.983	D	0.539	neutral	None	None	None	None	N
E/T	0.3847	ambiguous	0.4716	ambiguous	0.281	Stabilizing	0.998	D	0.577	neutral	None	None	None	None	N
E/V	0.4151	ambiguous	0.5042	ambiguous	-0.061	Destabilizing	0.999	D	0.663	neutral	N	0.520342835	None	None	N
E/W	0.9381	likely_pathogenic	0.9692	pathogenic	-0.192	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/Y	0.6826	likely_pathogenic	0.7942	pathogenic	-0.076	Destabilizing	1.0	D	0.674	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.