TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33677	101254;101255;101256	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
N2AB	32036	96331;96332;96333	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
N2A	31109	93550;93551;93552	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
N2B	24612	74059;74060;74061	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
Novex-1	24737	74434;74435;74436	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
Novex-2	24804	74635;74636;74637	chr2:178535586;178535585;178535584	chr2:179400313;179400312;179400311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-159
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.4872
• Predicted PPI site: I

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
I/T	rs1475771537	-0.1	0.949	N	0.475	0.207	0.608471955132	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/T	rs1475771537	-0.1	0.949	N	0.475	0.207	0.608471955132	gnomAD-4.0.0	3.18237E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71615E-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
I/A	0.7003	likely_pathogenic	0.5042	ambiguous	-0.611	Destabilizing	0.971	D	0.447	neutral	None	None	None	None	I
I/C	0.9252	likely_pathogenic	0.8511	pathogenic	-0.369	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	I
I/D	0.9662	likely_pathogenic	0.9087	pathogenic	-0.362	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	I
I/E	0.8996	likely_pathogenic	0.7723	pathogenic	-0.479	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	I
I/F	0.5002	ambiguous	0.3409	ambiguous	-0.816	Destabilizing	0.994	D	0.445	neutral	N	0.47493396	None	None	I
I/G	0.9433	likely_pathogenic	0.869	pathogenic	-0.76	Destabilizing	0.994	D	0.597	neutral	None	None	None	None	I
I/H	0.9285	likely_pathogenic	0.8254	pathogenic	-0.213	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
I/K	0.8718	likely_pathogenic	0.7251	pathogenic	-0.257	Destabilizing	0.944	D	0.599	neutral	None	None	None	None	I
I/L	0.291	likely_benign	0.2183	benign	-0.348	Destabilizing	0.246	N	0.187	neutral	N	0.469469426	None	None	I
I/M	0.1922	likely_benign	0.1362	benign	-0.234	Destabilizing	0.57	D	0.219	neutral	N	0.4563482	None	None	I
I/N	0.7527	likely_pathogenic	0.5441	ambiguous	0.071	Stabilizing	0.998	D	0.658	neutral	N	0.455212049	None	None	I
I/P	0.9776	likely_pathogenic	0.9575	pathogenic	-0.402	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
I/Q	0.8597	likely_pathogenic	0.7066	pathogenic	-0.218	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	I
I/R	0.8253	likely_pathogenic	0.656	pathogenic	0.31	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	I
I/S	0.6748	likely_pathogenic	0.4567	ambiguous	-0.319	Destabilizing	0.828	D	0.398	neutral	N	0.381194293	None	None	I
I/T	0.4661	ambiguous	0.2762	benign	-0.333	Destabilizing	0.949	D	0.475	neutral	N	0.424254424	None	None	I
I/V	0.1462	likely_benign	0.1116	benign	-0.402	Destabilizing	0.301	N	0.269	neutral	N	0.461754019	None	None	I
I/W	0.9445	likely_pathogenic	0.9047	pathogenic	-0.842	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
I/Y	0.8797	likely_pathogenic	0.7807	pathogenic	-0.563	Destabilizing	0.994	D	0.539	neutral	None	None	None	None	I

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.