TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22588	67987;67988;67989	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
N2AB	20947	63064;63065;63066	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
N2A	20020	60283;60284;60285	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
N2B	13523	40792;40793;40794	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
Novex-1	13648	41167;41168;41169	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
Novex-2	13715	41368;41369;41370	chr2:178579268;178579267;178579266	chr2:179443995;179443994;179443993
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-127
• Domain position: 29
• Structural Position: 52
• Q(SASA): 0.8855
• 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/K	None	None	0.978	N	0.49	0.312	0.309530620856	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85995E-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
E/A	0.122	likely_benign	0.123	benign	-0.059	Destabilizing	0.989	D	0.451	neutral	N	0.471004568	None	None	N
E/C	0.7293	likely_pathogenic	0.7369	pathogenic	0.029	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	N
E/D	0.069	likely_benign	0.068	benign	-0.102	Destabilizing	0.054	N	0.232	neutral	N	0.367375981	None	None	N
E/F	0.6332	likely_pathogenic	0.6396	pathogenic	-0.141	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
E/G	0.1169	likely_benign	0.1173	benign	-0.183	Destabilizing	0.978	D	0.462	neutral	N	0.354977113	None	None	N
E/H	0.3816	ambiguous	0.3955	ambiguous	0.335	Stabilizing	0.999	D	0.443	neutral	None	None	None	None	N
E/I	0.2412	likely_benign	0.2506	benign	0.209	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
E/K	0.1082	likely_benign	0.1182	benign	0.494	Stabilizing	0.978	D	0.49	neutral	N	0.445356762	None	None	N
E/L	0.3013	likely_benign	0.3113	benign	0.209	Stabilizing	0.998	D	0.56	neutral	None	None	None	None	N
E/M	0.3212	likely_benign	0.324	benign	0.124	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	N
E/N	0.1395	likely_benign	0.1368	benign	0.382	Stabilizing	0.983	D	0.439	neutral	None	None	None	None	N
E/P	0.337	likely_benign	0.3245	benign	0.138	Stabilizing	0.999	D	0.455	neutral	None	None	None	None	N
E/Q	0.1353	likely_benign	0.1392	benign	0.377	Stabilizing	0.989	D	0.448	neutral	N	0.450167936	None	None	N
E/R	0.2152	likely_benign	0.2287	benign	0.666	Stabilizing	0.998	D	0.463	neutral	None	None	None	None	N
E/S	0.1297	likely_benign	0.1272	benign	0.186	Stabilizing	0.983	D	0.465	neutral	None	None	None	None	N
E/T	0.1415	likely_benign	0.1377	benign	0.288	Stabilizing	0.992	D	0.431	neutral	None	None	None	None	N
E/V	0.1583	likely_benign	0.1662	benign	0.138	Stabilizing	0.999	D	0.475	neutral	N	0.501231474	None	None	N
E/W	0.7972	likely_pathogenic	0.8064	pathogenic	-0.094	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/Y	0.5193	ambiguous	0.5205	ambiguous	0.088	Stabilizing	0.999	D	0.521	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.