TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15145	45658;45659;45660	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
N2AB	13504	40735;40736;40737	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
N2A	12577	37954;37955;37956	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
N2B	6080	18463;18464;18465	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
Novex-1	6205	18838;18839;18840	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
Novex-2	6272	19039;19040;19041	chr2:178621285;178621284;178621283	chr2:179486012;179486011;179486010
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-103
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4037
• 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/E	None	None	0.939	N	0.497	0.254	0.418095516054	gnomAD-4.0.0	1.36966E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79987E-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	0.9021	likely_pathogenic	0.8085	pathogenic	-0.328	Destabilizing	0.953	D	0.413	neutral	None	None	None	None	N
K/C	0.977	likely_pathogenic	0.9493	pathogenic	-0.493	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
K/D	0.9764	likely_pathogenic	0.9419	pathogenic	0.181	Stabilizing	0.993	D	0.419	neutral	None	None	None	None	N
K/E	0.705	likely_pathogenic	0.545	ambiguous	0.259	Stabilizing	0.939	D	0.497	neutral	N	0.500026907	None	None	N
K/F	0.9906	likely_pathogenic	0.9808	pathogenic	-0.239	Destabilizing	0.993	D	0.572	neutral	None	None	None	None	N
K/G	0.9316	likely_pathogenic	0.8765	pathogenic	-0.608	Destabilizing	0.976	D	0.42	neutral	None	None	None	None	N
K/H	0.8392	likely_pathogenic	0.7432	pathogenic	-0.702	Destabilizing	0.128	N	0.34	neutral	None	None	None	None	N
K/I	0.897	likely_pathogenic	0.815	pathogenic	0.362	Stabilizing	0.991	D	0.574	neutral	N	0.507653325	None	None	N
K/L	0.8612	likely_pathogenic	0.7716	pathogenic	0.362	Stabilizing	0.986	D	0.412	neutral	None	None	None	None	N
K/M	0.7722	likely_pathogenic	0.6627	pathogenic	-0.015	Destabilizing	0.999	D	0.431	neutral	None	None	None	None	N
K/N	0.9402	likely_pathogenic	0.8772	pathogenic	-0.143	Destabilizing	0.982	D	0.445	neutral	N	0.508164819	None	None	N
K/P	0.9863	likely_pathogenic	0.9768	pathogenic	0.161	Stabilizing	0.998	D	0.441	neutral	None	None	None	None	N
K/Q	0.5359	ambiguous	0.3905	ambiguous	-0.187	Destabilizing	0.982	D	0.506	neutral	N	0.51069805	None	None	N
K/R	0.1742	likely_benign	0.1475	benign	-0.177	Destabilizing	0.046	N	0.273	neutral	N	0.493088865	None	None	N
K/S	0.9364	likely_pathogenic	0.8649	pathogenic	-0.729	Destabilizing	0.953	D	0.477	neutral	None	None	None	None	N
K/T	0.7624	likely_pathogenic	0.6223	pathogenic	-0.464	Destabilizing	0.991	D	0.417	neutral	N	0.509091612	None	None	N
K/V	0.8487	likely_pathogenic	0.7449	pathogenic	0.161	Stabilizing	0.993	D	0.491	neutral	None	None	None	None	N
K/W	0.9865	likely_pathogenic	0.9748	pathogenic	-0.2	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
K/Y	0.973	likely_pathogenic	0.9505	pathogenic	0.108	Stabilizing	0.986	D	0.498	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.