TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16198	48817;48818;48819	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
N2AB	14557	43894;43895;43896	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
N2A	13630	41113;41114;41115	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
N2B	7133	21622;21623;21624	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
Novex-1	7258	21997;21998;21999	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
Novex-2	7325	22198;22199;22200	chr2:178615353;178615352;178615351	chr2:179480080;179480079;179480078
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-5
• Domain position: 44
• Structural Position: 51
• Q(SASA): 0.6515
• 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/A	None	None	1.0	N	0.545	0.39	0.304435445954	gnomAD-4.0.0	1.36946E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80002E-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
G/A	0.4144	ambiguous	0.3572	ambiguous	-0.301	Destabilizing	1.0	D	0.545	neutral	N	0.520877807	None	None	N
G/C	0.5892	likely_pathogenic	0.5062	ambiguous	-0.949	Destabilizing	1.0	D	0.675	prob.neutral	D	0.682378772	None	None	N
G/D	0.3083	likely_benign	0.2622	benign	-0.703	Destabilizing	1.0	D	0.568	neutral	D	0.53047557	None	None	N
G/E	0.4834	ambiguous	0.4262	ambiguous	-0.859	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
G/F	0.8502	likely_pathogenic	0.813	pathogenic	-1.083	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
G/H	0.7067	likely_pathogenic	0.6347	pathogenic	-0.382	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
G/I	0.7585	likely_pathogenic	0.6724	pathogenic	-0.564	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
G/K	0.8298	likely_pathogenic	0.7628	pathogenic	-0.729	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
G/L	0.7742	likely_pathogenic	0.727	pathogenic	-0.564	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
G/M	0.81	likely_pathogenic	0.765	pathogenic	-0.704	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
G/N	0.3831	ambiguous	0.3453	ambiguous	-0.39	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	N
G/P	0.9525	likely_pathogenic	0.9293	pathogenic	-0.453	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
G/Q	0.6725	likely_pathogenic	0.607	pathogenic	-0.662	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
G/R	0.7778	likely_pathogenic	0.6998	pathogenic	-0.301	Destabilizing	1.0	D	0.618	neutral	D	0.533288027	None	None	N
G/S	0.2441	likely_benign	0.2072	benign	-0.52	Destabilizing	1.0	D	0.615	neutral	N	0.468359606	None	None	N
G/T	0.4663	ambiguous	0.3957	ambiguous	-0.618	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
G/V	0.6507	likely_pathogenic	0.5541	ambiguous	-0.453	Destabilizing	1.0	D	0.663	neutral	D	0.59865995	None	None	N
G/W	0.7737	likely_pathogenic	0.6977	pathogenic	-1.174	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
G/Y	0.7309	likely_pathogenic	0.6696	pathogenic	-0.878	Destabilizing	1.0	D	0.643	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.