TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18251	54976;54977;54978	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
N2AB	16610	50053;50054;50055	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
N2A	15683	47272;47273;47274	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
N2B	9186	27781;27782;27783	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
Novex-1	9311	28156;28157;28158	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
Novex-2	9378	28357;28358;28359	chr2:178603936;178603935;178603934	chr2:179468663;179468662;179468661
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-20
• Domain position: 86
• Structural Position: 113
• Q(SASA): 0.619
• Predicted PPI site: I

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
A/T	None	None	0.669	N	0.249	0.183	0.250579442822	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5324	ambiguous	0.5587	ambiguous	-0.807	Destabilizing	0.998	D	0.262	neutral	None	None	None	None	I
A/D	0.4744	ambiguous	0.4804	ambiguous	-0.639	Destabilizing	0.934	D	0.469	neutral	N	0.461588156	None	None	I
A/E	0.3411	ambiguous	0.3564	ambiguous	-0.804	Destabilizing	0.842	D	0.365	neutral	None	None	None	None	I
A/F	0.477	ambiguous	0.4152	ambiguous	-0.97	Destabilizing	0.949	D	0.487	neutral	None	None	None	None	I
A/G	0.2074	likely_benign	0.1989	benign	-0.245	Destabilizing	0.801	D	0.232	neutral	N	0.513550198	None	None	I
A/H	0.5059	ambiguous	0.5232	ambiguous	-0.242	Destabilizing	0.998	D	0.454	neutral	None	None	None	None	I
A/I	0.2329	likely_benign	0.1873	benign	-0.433	Destabilizing	0.016	N	0.181	neutral	None	None	None	None	I
A/K	0.4382	ambiguous	0.4691	ambiguous	-0.52	Destabilizing	0.842	D	0.361	neutral	None	None	None	None	I
A/L	0.1704	likely_benign	0.1423	benign	-0.433	Destabilizing	0.016	N	0.189	neutral	None	None	None	None	I
A/M	0.2172	likely_benign	0.1811	benign	-0.427	Destabilizing	0.949	D	0.356	neutral	None	None	None	None	I
A/N	0.31	likely_benign	0.2888	benign	-0.273	Destabilizing	0.949	D	0.484	neutral	None	None	None	None	I
A/P	0.5212	ambiguous	0.5467	ambiguous	-0.342	Destabilizing	0.966	D	0.373	neutral	N	0.506341798	None	None	I
A/Q	0.3152	likely_benign	0.335	benign	-0.588	Destabilizing	0.974	D	0.365	neutral	None	None	None	None	I
A/R	0.4124	ambiguous	0.4524	ambiguous	-0.028	Destabilizing	0.974	D	0.364	neutral	None	None	None	None	I
A/S	0.1173	likely_benign	0.1206	benign	-0.423	Destabilizing	0.062	N	0.089	neutral	N	0.444079831	None	None	I
A/T	0.1021	likely_benign	0.0963	benign	-0.52	Destabilizing	0.669	D	0.249	neutral	N	0.503088062	None	None	I
A/V	0.1285	likely_benign	0.1093	benign	-0.342	Destabilizing	0.454	N	0.293	neutral	N	0.499549111	None	None	I
A/W	0.8371	likely_pathogenic	0.8297	pathogenic	-1.063	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	I
A/Y	0.5654	likely_pathogenic	0.5516	ambiguous	-0.731	Destabilizing	0.974	D	0.485	neutral	None	None	None	None	I

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.