TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6486	19681;19682;19683	chr2:178728368;178728367;178728366	chr2:179593095;179593094;179593093
N2AB	6169	18730;18731;18732	chr2:178728368;178728367;178728366	chr2:179593095;179593094;179593093
N2A	5242	15949;15950;15951	chr2:178728368;178728367;178728366	chr2:179593095;179593094;179593093
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-49
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4083
• 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
K/Q	None	None	0.884	D	0.451	0.261	0.290962096972	gnomAD-4.0.0	1.619E-06	None	None	None	None	N	None	0	0	None	0	2.79002E-05	None	0	0	0	0	0
K/R	rs1168625867	-0.262	0.007	N	0.183	0.187	0.297718772494	gnomAD-2.1.1	4.26E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.37E-06	0
K/R	rs1168625867	-0.262	0.007	N	0.183	0.187	0.297718772494	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1168625867	-0.262	0.007	N	0.183	0.187	0.297718772494	gnomAD-4.0.0	6.8615E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.35691E-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
K/A	0.3462	ambiguous	0.4211	ambiguous	-0.469	Destabilizing	0.543	D	0.419	neutral	None	None	None	None	N
K/C	0.7484	likely_pathogenic	0.829	pathogenic	-0.43	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
K/D	0.5825	likely_pathogenic	0.6692	pathogenic	0.36	Stabilizing	0.854	D	0.491	neutral	None	None	None	None	N
K/E	0.2136	likely_benign	0.2464	benign	0.454	Stabilizing	0.684	D	0.381	neutral	N	0.484251206	None	None	N
K/F	0.754	likely_pathogenic	0.8073	pathogenic	-0.26	Destabilizing	0.984	D	0.552	neutral	None	None	None	None	N
K/G	0.4432	ambiguous	0.5143	ambiguous	-0.787	Destabilizing	0.004	N	0.297	neutral	None	None	None	None	N
K/H	0.326	likely_benign	0.4098	ambiguous	-0.972	Destabilizing	0.953	D	0.507	neutral	None	None	None	None	N
K/I	0.3804	ambiguous	0.4313	ambiguous	0.336	Stabilizing	0.939	D	0.568	neutral	N	0.514116613	None	None	N
K/L	0.3697	ambiguous	0.4339	ambiguous	0.336	Stabilizing	0.742	D	0.554	neutral	None	None	None	None	N
K/M	0.2186	likely_benign	0.2549	benign	0.085	Stabilizing	0.996	D	0.503	neutral	None	None	None	None	N
K/N	0.35	ambiguous	0.4373	ambiguous	-0.089	Destabilizing	0.684	D	0.425	neutral	N	0.519511891	None	None	N
K/P	0.358	ambiguous	0.4388	ambiguous	0.097	Stabilizing	0.004	N	0.207	neutral	None	None	None	None	N
K/Q	0.1329	likely_benign	0.1577	benign	-0.141	Destabilizing	0.884	D	0.451	neutral	D	0.529211162	None	None	N
K/R	0.0889	likely_benign	0.0953	benign	-0.249	Destabilizing	0.007	N	0.183	neutral	N	0.493076297	None	None	N
K/S	0.3951	ambiguous	0.4952	ambiguous	-0.773	Destabilizing	0.742	D	0.366	neutral	None	None	None	None	N
K/T	0.1758	likely_benign	0.2085	benign	-0.478	Destabilizing	0.684	D	0.465	neutral	N	0.494886723	None	None	N
K/V	0.3629	ambiguous	0.4157	ambiguous	0.097	Stabilizing	0.854	D	0.542	neutral	None	None	None	None	N
K/W	0.787	likely_pathogenic	0.8257	pathogenic	-0.149	Destabilizing	0.996	D	0.636	neutral	None	None	None	None	N
K/Y	0.5794	likely_pathogenic	0.6544	pathogenic	0.138	Stabilizing	0.984	D	0.557	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.