TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9408	28447;28448;28449	chr2:178710875;178710874;178710873	chr2:179575602;179575601;179575600
N2AB	9091	27496;27497;27498	chr2:178710875;178710874;178710873	chr2:179575602;179575601;179575600
N2A	8164	24715;24716;24717	chr2:178710875;178710874;178710873	chr2:179575602;179575601;179575600
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-80
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2073
• 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
A/T	rs767417518	-1.35	0.722	None	0.525	0.284	0.366659145958	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65948E-04
A/T	rs767417518	-1.35	0.722	None	0.525	0.284	0.366659145958	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs767417518	-1.35	0.722	None	0.525	0.284	0.366659145958	gnomAD-4.0.0	3.04472E-06	None	None	None	None	N	None	3.49369E-05	0	None	0	0	None	0	0	1.20491E-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	0.3695	ambiguous	0.4193	ambiguous	-1.089	Destabilizing	0.996	D	0.563	neutral	None	None	None	None	N
A/D	0.436	ambiguous	0.4626	ambiguous	-1.829	Destabilizing	0.949	D	0.609	neutral	None	None	None	None	N
A/E	0.3604	ambiguous	0.3884	ambiguous	-1.832	Destabilizing	0.961	D	0.612	neutral	None	None	None	None	N
A/F	0.3723	ambiguous	0.3881	ambiguous	-1.158	Destabilizing	0.923	D	0.629	neutral	None	None	None	None	N
A/G	0.1159	likely_benign	0.1323	benign	-1.482	Destabilizing	0.008	N	0.186	neutral	None	None	None	None	N
A/H	0.5355	ambiguous	0.6025	pathogenic	-1.685	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
A/I	0.1992	likely_benign	0.2564	benign	-0.511	Destabilizing	0.372	N	0.501	neutral	None	None	None	None	N
A/K	0.4602	ambiguous	0.5128	ambiguous	-1.545	Destabilizing	0.961	D	0.615	neutral	None	None	None	None	N
A/L	0.1716	likely_benign	0.2114	benign	-0.511	Destabilizing	0.415	N	0.506	neutral	None	None	None	None	N
A/M	0.2034	likely_benign	0.2573	benign	-0.392	Destabilizing	0.923	D	0.612	neutral	None	None	None	None	N
A/N	0.3543	ambiguous	0.3943	ambiguous	-1.298	Destabilizing	0.923	D	0.637	neutral	None	None	None	None	N
A/P	0.5981	likely_pathogenic	0.667	pathogenic	-0.696	Destabilizing	0.983	D	0.621	neutral	None	None	None	None	N
A/Q	0.4242	ambiguous	0.474	ambiguous	-1.442	Destabilizing	0.987	D	0.617	neutral	None	None	None	None	N
A/R	0.3705	ambiguous	0.4154	ambiguous	-1.173	Destabilizing	0.961	D	0.64	neutral	None	None	None	None	N
A/S	0.1154	likely_benign	0.1282	benign	-1.626	Destabilizing	0.722	D	0.518	neutral	None	None	None	None	N
A/T	0.0852	likely_benign	0.1085	benign	-1.542	Destabilizing	0.722	D	0.525	neutral	None	None	None	None	N
A/V	0.0974	likely_benign	0.1264	benign	-0.696	Destabilizing	0.003	N	0.159	neutral	None	None	None	None	N
A/W	0.7606	likely_pathogenic	0.7991	pathogenic	-1.565	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
A/Y	0.5295	ambiguous	0.5669	pathogenic	-1.18	Destabilizing	0.961	D	0.621	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.