TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4674	14245;14246;14247	chr2:178739213;178739212;178739211	chr2:179603940;179603939;179603938
N2AB	4357	13294;13295;13296	chr2:178739213;178739212;178739211	chr2:179603940;179603939;179603938
N2A	None	None	chr2:None	chr2:None
N2B	4311	13156;13157;13158	chr2:178739213;178739212;178739211	chr2:179603940;179603939;179603938
Novex-1	4436	13531;13532;13533	chr2:178739213;178739212;178739211	chr2:179603940;179603939;179603938
Novex-2	4503	13732;13733;13734	chr2:178739213;178739212;178739211	chr2:179603940;179603939;179603938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-29
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.583
• 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/D	rs761849101	-0.797	0.001	D	0.313	0.181	None	gnomAD-2.1.1	4.66E-06	None	None	None	None	N	None	0	0	None	0	5.77E-05	None	0	None	0	0	0
E/D	rs761849101	-0.797	0.001	D	0.313	0.181	None	gnomAD-4.0.0	7.09787E-07	None	None	None	None	N	None	3.09809E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs1196320491	-0.553	0.002	D	0.325	0.144	None	gnomAD-2.1.1	4.59E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	5.21E-05	0	0
E/Q	rs1196320491	-0.553	0.002	D	0.325	0.144	None	gnomAD-4.0.0	1.72318E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.95351E-05	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	0.1176	likely_benign	0.0991	benign	-1.059	Destabilizing	0.001	N	0.389	neutral	D	0.55875195	None	None	N
E/C	0.6941	likely_pathogenic	0.6742	pathogenic	-0.473	Destabilizing	0.909	D	0.745	deleterious	None	None	None	None	N
E/D	0.1036	likely_benign	0.1187	benign	-0.954	Destabilizing	0.001	N	0.313	neutral	D	0.591898832	None	None	N
E/F	0.4729	ambiguous	0.4518	ambiguous	-0.284	Destabilizing	0.726	D	0.749	deleterious	None	None	None	None	N
E/G	0.146	likely_benign	0.146	benign	-1.44	Destabilizing	0.124	N	0.628	neutral	D	0.70339072	None	None	N
E/H	0.3009	likely_benign	0.2925	benign	-0.408	Destabilizing	0.567	D	0.633	neutral	None	None	None	None	N
E/I	0.1864	likely_benign	0.1683	benign	-0.008	Destabilizing	0.567	D	0.756	deleterious	None	None	None	None	N
E/K	0.0926	likely_benign	0.0887	benign	-0.388	Destabilizing	0.124	N	0.576	neutral	N	0.499551229	None	None	N
E/L	0.225	likely_benign	0.2038	benign	-0.008	Destabilizing	0.396	N	0.683	prob.neutral	None	None	None	None	N
E/M	0.2598	likely_benign	0.231	benign	0.462	Stabilizing	0.909	D	0.742	deleterious	None	None	None	None	N
E/N	0.1423	likely_benign	0.1477	benign	-1.033	Destabilizing	0.396	N	0.595	neutral	None	None	None	None	N
E/P	0.5252	ambiguous	0.4856	ambiguous	-0.339	Destabilizing	0.567	D	0.713	prob.delet.	None	None	None	None	N
E/Q	0.1117	likely_benign	0.1029	benign	-0.891	Destabilizing	0.002	N	0.325	neutral	D	0.533919147	None	None	N
E/R	0.161	likely_benign	0.1522	benign	-0.072	Destabilizing	0.396	N	0.605	neutral	None	None	None	None	N
E/S	0.139	likely_benign	0.1301	benign	-1.369	Destabilizing	0.157	N	0.567	neutral	None	None	None	None	N
E/T	0.133	likely_benign	0.1147	benign	-1.032	Destabilizing	0.157	N	0.627	neutral	None	None	None	None	N
E/V	0.1378	likely_benign	0.126	benign	-0.339	Destabilizing	0.331	N	0.68	prob.neutral	N	0.510046502	None	None	N
E/W	0.7097	likely_pathogenic	0.7046	pathogenic	0.118	Stabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.3782	ambiguous	0.3654	ambiguous	0.037	Stabilizing	0.726	D	0.75	deleterious	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.