TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3130	9613;9614;9615	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
N2AB	3130	9613;9614;9615	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
N2A	3130	9613;9614;9615	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
N2B	3084	9475;9476;9477	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
Novex-1	3084	9475;9476;9477	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
Novex-2	3084	9475;9476;9477	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567
Novex-3	3130	9613;9614;9615	chr2:178767842;178767841;178767840	chr2:179632569;179632568;179632567

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-21
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.2258
• 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/A	None	None	0.999	D	0.639	0.511	0.715916371082	gnomAD-4.0.0	1.59051E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85646E-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	0.3961	ambiguous	0.4463	ambiguous	-1.482	Destabilizing	0.999	D	0.639	neutral	D	0.589871917	None	None	N
V/C	0.9212	likely_pathogenic	0.9071	pathogenic	-1.031	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/D	0.892	likely_pathogenic	0.9014	pathogenic	-1.286	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/E	0.6974	likely_pathogenic	0.6939	pathogenic	-1.2	Destabilizing	1.0	D	0.832	deleterious	N	0.511665423	None	None	N
V/F	0.3143	likely_benign	0.3457	ambiguous	-0.913	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/G	0.6722	likely_pathogenic	0.7123	pathogenic	-1.888	Destabilizing	1.0	D	0.829	deleterious	D	0.646081934	None	None	N
V/H	0.8441	likely_pathogenic	0.8288	pathogenic	-1.487	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.1012	likely_benign	0.1043	benign	-0.434	Destabilizing	0.998	D	0.57	neutral	None	None	None	None	N
V/K	0.688	likely_pathogenic	0.6651	pathogenic	-1.199	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/L	0.3797	ambiguous	0.3836	ambiguous	-0.434	Destabilizing	0.997	D	0.601	neutral	N	0.503229222	None	None	N
V/M	0.243	likely_benign	0.2567	benign	-0.427	Destabilizing	1.0	D	0.743	deleterious	D	0.564338338	None	None	N
V/N	0.7411	likely_pathogenic	0.7574	pathogenic	-1.159	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/P	0.99	likely_pathogenic	0.9908	pathogenic	-0.749	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Q	0.653	likely_pathogenic	0.6367	pathogenic	-1.187	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/R	0.617	likely_pathogenic	0.5932	pathogenic	-0.867	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/S	0.5177	ambiguous	0.5637	ambiguous	-1.774	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/T	0.37	ambiguous	0.4	ambiguous	-1.565	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
V/W	0.9411	likely_pathogenic	0.9354	pathogenic	-1.233	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/Y	0.7858	likely_pathogenic	0.8016	pathogenic	-0.871	Destabilizing	1.0	D	0.837	deleterious	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.