TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21614	65065;65066;65067	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
N2AB	19973	60142;60143;60144	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
N2A	19046	57361;57362;57363	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
N2B	12549	37870;37871;37872	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
Novex-1	12674	38245;38246;38247	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
Novex-2	12741	38446;38447;38448	chr2:178584801;178584800;178584799	chr2:179449528;179449527;179449526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-44
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1073
• 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
V/F	rs1255799944	-1.624	0.998	N	0.677	0.368	0.691676124756	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/F	rs1255799944	-1.624	0.998	N	0.677	0.368	0.691676124756	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	2.23654E-05	None	0	0	None	0	0	8.99622E-07	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
V/A	0.3764	ambiguous	0.4624	ambiguous	-1.743	Destabilizing	0.91	D	0.58	neutral	N	0.473162302	None	None	N
V/C	0.7991	likely_pathogenic	0.7883	pathogenic	-1.333	Destabilizing	0.092	N	0.395	neutral	None	None	None	None	N
V/D	0.9553	likely_pathogenic	0.9686	pathogenic	-1.636	Destabilizing	0.998	D	0.742	deleterious	N	0.485470114	None	None	N
V/E	0.9084	likely_pathogenic	0.9311	pathogenic	-1.466	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
V/F	0.6934	likely_pathogenic	0.7243	pathogenic	-1.041	Destabilizing	0.998	D	0.677	prob.neutral	N	0.485674378	None	None	N
V/G	0.6228	likely_pathogenic	0.6857	pathogenic	-2.244	Highly Destabilizing	0.994	D	0.725	prob.delet.	N	0.518822731	None	None	N
V/H	0.9639	likely_pathogenic	0.9697	pathogenic	-1.895	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/I	0.1188	likely_benign	0.1285	benign	-0.383	Destabilizing	0.954	D	0.616	neutral	N	0.474093306	None	None	N
V/K	0.939	likely_pathogenic	0.9494	pathogenic	-1.262	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
V/L	0.5531	ambiguous	0.5938	pathogenic	-0.383	Destabilizing	0.91	D	0.593	neutral	N	0.499180965	None	None	N
V/M	0.3965	ambiguous	0.4707	ambiguous	-0.459	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
V/N	0.7677	likely_pathogenic	0.8056	pathogenic	-1.404	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/P	0.9549	likely_pathogenic	0.9616	pathogenic	-0.805	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
V/Q	0.8569	likely_pathogenic	0.8813	pathogenic	-1.307	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
V/R	0.9244	likely_pathogenic	0.9325	pathogenic	-1.104	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
V/S	0.5355	ambiguous	0.5922	pathogenic	-2.12	Highly Destabilizing	0.985	D	0.694	prob.neutral	None	None	None	None	N
V/T	0.4497	ambiguous	0.5264	ambiguous	-1.801	Destabilizing	0.985	D	0.632	neutral	None	None	None	None	N
V/W	0.9922	likely_pathogenic	0.9932	pathogenic	-1.428	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/Y	0.9532	likely_pathogenic	0.9557	pathogenic	-1.038	Destabilizing	0.999	D	0.669	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.