TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30169	90730;90731;90732	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
N2AB	28528	85807;85808;85809	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
N2A	27601	83026;83027;83028	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
N2B	21104	63535;63536;63537	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
Novex-1	21229	63910;63911;63912	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
Novex-2	21296	64111;64112;64113	chr2:178552395;178552394;178552393	chr2:179417122;179417121;179417120
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-148
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3901
• 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
G/D	rs775893072	-0.72	0.001	N	0.215	0.206	None	gnomAD-2.1.1	3.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	7.45E-05	0
G/D	rs775893072	-0.72	0.001	N	0.215	0.206	None	gnomAD-4.0.0	9.03258E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.09214E-05	0	1.68623E-05
G/V	None	None	0.627	N	0.512	0.24	0.531825494424	gnomAD-4.0.0	6.94814E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.1012E-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
G/A	0.1689	likely_benign	0.1879	benign	-0.291	Destabilizing	0.09	N	0.347	neutral	N	0.50716573	None	None	N
G/C	0.2021	likely_benign	0.2565	benign	-0.888	Destabilizing	0.928	D	0.477	neutral	N	0.481128474	None	None	N
G/D	0.128	likely_benign	0.1499	benign	-0.504	Destabilizing	0.001	N	0.215	neutral	N	0.432627899	None	None	N
G/E	0.1876	likely_benign	0.222	benign	-0.645	Destabilizing	0.241	N	0.35	neutral	None	None	None	None	N
G/F	0.5959	likely_pathogenic	0.6372	pathogenic	-0.884	Destabilizing	0.818	D	0.474	neutral	None	None	None	None	N
G/H	0.3184	likely_benign	0.3648	ambiguous	-0.507	Destabilizing	0.69	D	0.425	neutral	None	None	None	None	N
G/I	0.3697	ambiguous	0.3977	ambiguous	-0.345	Destabilizing	0.69	D	0.489	neutral	None	None	None	None	N
G/K	0.4224	ambiguous	0.4415	ambiguous	-0.894	Destabilizing	0.241	N	0.395	neutral	None	None	None	None	N
G/L	0.4438	ambiguous	0.5144	ambiguous	-0.345	Destabilizing	0.388	N	0.51	neutral	None	None	None	None	N
G/M	0.4513	ambiguous	0.5118	ambiguous	-0.481	Destabilizing	0.981	D	0.463	neutral	None	None	None	None	N
G/N	0.1293	likely_benign	0.1504	benign	-0.57	Destabilizing	0.001	N	0.121	neutral	None	None	None	None	N
G/P	0.9139	likely_pathogenic	0.912	pathogenic	-0.292	Destabilizing	0.818	D	0.449	neutral	None	None	None	None	N
G/Q	0.2637	likely_benign	0.3035	benign	-0.811	Destabilizing	0.69	D	0.453	neutral	None	None	None	None	N
G/R	0.3421	ambiguous	0.3543	ambiguous	-0.457	Destabilizing	0.627	D	0.459	neutral	N	0.520729673	None	None	N
G/S	0.0874	likely_benign	0.0963	benign	-0.745	Destabilizing	0.001	N	0.161	neutral	N	0.51555314	None	None	N
G/T	0.1673	likely_benign	0.1927	benign	-0.808	Destabilizing	0.241	N	0.373	neutral	None	None	None	None	N
G/V	0.2939	likely_benign	0.3334	benign	-0.292	Destabilizing	0.627	D	0.512	neutral	N	0.481128474	None	None	N
G/W	0.5129	ambiguous	0.5872	pathogenic	-1.075	Destabilizing	0.981	D	0.507	neutral	None	None	None	None	N
G/Y	0.4037	ambiguous	0.4647	ambiguous	-0.719	Destabilizing	0.818	D	0.474	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.