TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29776	89551;89552;89553	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
N2AB	28135	84628;84629;84630	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
N2A	27208	81847;81848;81849	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
N2B	20711	62356;62357;62358	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
Novex-1	20836	62731;62732;62733	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
Novex-2	20903	62932;62933;62934	chr2:178553679;178553678;178553677	chr2:179418406;179418405;179418404
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-105
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2356
• 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/E	None	None	0.012	N	0.535	0.085	0.17948927462	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.1244	likely_benign	0.1244	benign	-0.692	Destabilizing	0.022	N	0.243	neutral	N	0.432398613	None	None	N
G/C	0.2646	likely_benign	0.2684	benign	-0.753	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
G/D	0.1746	likely_benign	0.1705	benign	-1.223	Destabilizing	0.728	D	0.581	neutral	None	None	None	None	N
G/E	0.1678	likely_benign	0.1694	benign	-1.294	Destabilizing	0.012	N	0.535	neutral	N	0.418045236	None	None	N
G/F	0.636	likely_pathogenic	0.6466	pathogenic	-1.012	Destabilizing	0.949	D	0.69	prob.neutral	None	None	None	None	N
G/H	0.4401	ambiguous	0.4536	ambiguous	-1.341	Destabilizing	0.993	D	0.62	neutral	None	None	None	None	N
G/I	0.3169	likely_benign	0.3434	ambiguous	-0.36	Destabilizing	0.904	D	0.669	neutral	None	None	None	None	N
G/K	0.3722	ambiguous	0.3909	ambiguous	-1.366	Destabilizing	0.728	D	0.615	neutral	None	None	None	None	N
G/L	0.3693	ambiguous	0.3873	ambiguous	-0.36	Destabilizing	0.016	N	0.578	neutral	None	None	None	None	N
G/M	0.4222	ambiguous	0.4492	ambiguous	-0.27	Destabilizing	0.949	D	0.649	neutral	None	None	None	None	N
G/N	0.2422	likely_benign	0.2445	benign	-0.913	Destabilizing	0.842	D	0.586	neutral	None	None	None	None	N
G/P	0.6262	likely_pathogenic	0.6493	pathogenic	-0.431	Destabilizing	0.974	D	0.652	neutral	None	None	None	None	N
G/Q	0.326	likely_benign	0.3431	ambiguous	-1.113	Destabilizing	0.904	D	0.658	neutral	None	None	None	None	N
G/R	0.3348	likely_benign	0.3448	ambiguous	-0.994	Destabilizing	0.934	D	0.653	neutral	N	0.460009288	None	None	N
G/S	0.1185	likely_benign	0.1183	benign	-1.111	Destabilizing	0.172	N	0.401	neutral	None	None	None	None	N
G/T	0.1746	likely_benign	0.1811	benign	-1.114	Destabilizing	0.067	N	0.535	neutral	None	None	None	None	N
G/V	0.2159	likely_benign	0.2284	benign	-0.431	Destabilizing	0.669	D	0.636	neutral	N	0.434033408	None	None	N
G/W	0.4568	ambiguous	0.4778	ambiguous	-1.376	Destabilizing	0.998	D	0.641	neutral	None	None	None	None	N
G/Y	0.4697	ambiguous	0.4789	ambiguous	-0.986	Destabilizing	0.991	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.