TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15042	45349;45350;45351	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
N2AB	13401	40426;40427;40428	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
N2A	12474	37645;37646;37647	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
N2B	5977	18154;18155;18156	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
Novex-1	6102	18529;18530;18531	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
Novex-2	6169	18730;18731;18732	chr2:178621700;178621699;178621698	chr2:179486427;179486426;179486425
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-102
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1537
• 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/I	None	None	0.324	N	0.439	0.26	0.625329643188	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
V/A	0.2007	likely_benign	0.243	benign	-1.885	Destabilizing	None	N	0.135	neutral	N	0.466112578	None	None	N
V/C	0.8486	likely_pathogenic	0.8994	pathogenic	-1.314	Destabilizing	0.944	D	0.534	neutral	None	None	None	None	N
V/D	0.7157	likely_pathogenic	0.7887	pathogenic	-2.112	Highly Destabilizing	0.773	D	0.605	neutral	D	0.748399274	None	None	N
V/E	0.6697	likely_pathogenic	0.7475	pathogenic	-2.062	Highly Destabilizing	0.388	N	0.533	neutral	None	None	None	None	N
V/F	0.3794	ambiguous	0.4356	ambiguous	-1.408	Destabilizing	0.773	D	0.581	neutral	D	0.613706367	None	None	N
V/G	0.2202	likely_benign	0.284	benign	-2.271	Highly Destabilizing	None	N	0.292	neutral	D	0.528894982	None	None	N
V/H	0.8798	likely_pathogenic	0.9263	pathogenic	-1.889	Destabilizing	0.981	D	0.556	neutral	None	None	None	None	N
V/I	0.1185	likely_benign	0.1224	benign	-0.886	Destabilizing	0.324	N	0.439	neutral	N	0.52179422	None	None	N
V/K	0.6685	likely_pathogenic	0.7913	pathogenic	-1.602	Destabilizing	0.388	N	0.533	neutral	None	None	None	None	N
V/L	0.4295	ambiguous	0.5087	ambiguous	-0.886	Destabilizing	0.09	N	0.422	neutral	D	0.59051797	None	None	N
V/M	0.3039	likely_benign	0.3337	benign	-0.657	Destabilizing	0.818	D	0.523	neutral	None	None	None	None	N
V/N	0.5755	likely_pathogenic	0.6704	pathogenic	-1.484	Destabilizing	0.818	D	0.603	neutral	None	None	None	None	N
V/P	0.9439	likely_pathogenic	0.9719	pathogenic	-1.187	Destabilizing	0.818	D	0.575	neutral	None	None	None	None	N
V/Q	0.6947	likely_pathogenic	0.7877	pathogenic	-1.605	Destabilizing	0.818	D	0.565	neutral	None	None	None	None	N
V/R	0.6576	likely_pathogenic	0.7803	pathogenic	-1.107	Destabilizing	0.69	D	0.593	neutral	None	None	None	None	N
V/S	0.3696	ambiguous	0.4462	ambiguous	-2.022	Highly Destabilizing	0.116	N	0.443	neutral	None	None	None	None	N
V/T	0.2519	likely_benign	0.3	benign	-1.861	Destabilizing	0.388	N	0.397	neutral	None	None	None	None	N
V/W	0.9619	likely_pathogenic	0.9773	pathogenic	-1.71	Destabilizing	0.981	D	0.559	neutral	None	None	None	None	N
V/Y	0.8277	likely_pathogenic	0.8746	pathogenic	-1.417	Destabilizing	0.932	D	0.585	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.