TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13750	41473;41474;41475	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
N2AB	12109	36550;36551;36552	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
N2A	11182	33769;33770;33771	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
N2B	4685	14278;14279;14280	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
Novex-1	4810	14653;14654;14655	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
Novex-2	4877	14854;14855;14856	chr2:178636479;178636478;178636477	chr2:179501206;179501205;179501204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-87
• Domain position: 67
• Structural Position: 146
• Q(SASA): 0.5854
• 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
L/F	None	None	1.0	N	0.61	0.338	0.493494165309	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
L/A	0.3823	ambiguous	0.4031	ambiguous	-0.881	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	I
L/C	0.7959	likely_pathogenic	0.8535	pathogenic	-0.864	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
L/D	0.8547	likely_pathogenic	0.8584	pathogenic	-0.066	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
L/E	0.5524	ambiguous	0.5553	ambiguous	-0.091	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/F	0.3107	likely_benign	0.344	ambiguous	-0.612	Destabilizing	1.0	D	0.61	neutral	N	0.448401997	None	None	I
L/G	0.7344	likely_pathogenic	0.7493	pathogenic	-1.113	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
L/H	0.4667	ambiguous	0.5167	ambiguous	-0.247	Destabilizing	1.0	D	0.675	prob.neutral	N	0.472401436	None	None	I
L/I	0.1153	likely_benign	0.1326	benign	-0.352	Destabilizing	0.999	D	0.385	neutral	N	0.434363586	None	None	I
L/K	0.368	ambiguous	0.393	ambiguous	-0.501	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
L/M	0.1785	likely_benign	0.1898	benign	-0.588	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
L/N	0.5726	likely_pathogenic	0.5738	pathogenic	-0.402	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
L/P	0.3217	likely_benign	0.3042	benign	-0.496	Destabilizing	1.0	D	0.695	prob.neutral	N	0.450419342	None	None	I
L/Q	0.2845	likely_benign	0.3045	benign	-0.508	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
L/R	0.3269	likely_benign	0.3755	ambiguous	-0.04	Destabilizing	1.0	D	0.699	prob.neutral	N	0.450407411	None	None	I
L/S	0.4953	ambiguous	0.5415	ambiguous	-0.964	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
L/T	0.3646	ambiguous	0.3884	ambiguous	-0.862	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
L/V	0.1211	likely_benign	0.1431	benign	-0.496	Destabilizing	0.999	D	0.423	neutral	N	0.452008409	None	None	I
L/W	0.5625	ambiguous	0.6241	pathogenic	-0.632	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
L/Y	0.5959	likely_pathogenic	0.6332	pathogenic	-0.399	Destabilizing	1.0	D	0.669	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.