TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9652	29179;29180;29181	chr2:178707613;178707612;178707611	chr2:179572340;179572339;179572338
N2AB	9335	28228;28229;28230	chr2:178707613;178707612;178707611	chr2:179572340;179572339;179572338
N2A	8408	25447;25448;25449	chr2:178707613;178707612;178707611	chr2:179572340;179572339;179572338
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-82
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0997
• 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/M	None	None	0.317	None	0.549	0.252	0.468168183122	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1191	likely_benign	0.1109	benign	-1.938	Destabilizing	None	N	0.164	neutral	None	None	None	None	N
V/C	0.8239	likely_pathogenic	0.8188	pathogenic	-1.747	Destabilizing	0.824	D	0.559	neutral	None	None	None	None	N
V/D	0.8651	likely_pathogenic	0.8405	pathogenic	-2.492	Highly Destabilizing	0.38	N	0.629	neutral	None	None	None	None	N
V/E	0.826	likely_pathogenic	0.7957	pathogenic	-2.424	Highly Destabilizing	0.317	N	0.6	neutral	None	None	None	None	N
V/F	0.5478	ambiguous	0.4937	ambiguous	-1.418	Destabilizing	0.38	N	0.621	neutral	None	None	None	None	N
V/G	0.3287	likely_benign	0.3036	benign	-2.321	Highly Destabilizing	0.062	N	0.565	neutral	None	None	None	None	N
V/H	0.9404	likely_pathogenic	0.9241	pathogenic	-1.779	Destabilizing	0.935	D	0.567	neutral	None	None	None	None	N
V/I	0.122	likely_benign	0.0991	benign	-0.936	Destabilizing	None	N	0.167	neutral	None	None	None	None	N
V/K	0.8539	likely_pathogenic	0.8355	pathogenic	-1.574	Destabilizing	0.149	N	0.598	neutral	None	None	None	None	N
V/L	0.4101	ambiguous	0.3379	benign	-0.936	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
V/M	0.3392	likely_benign	0.2472	benign	-0.95	Destabilizing	0.317	N	0.549	neutral	None	None	None	None	N
V/N	0.6762	likely_pathogenic	0.6685	pathogenic	-1.625	Destabilizing	0.38	N	0.628	neutral	None	None	None	None	N
V/P	0.7097	likely_pathogenic	0.6765	pathogenic	-1.24	Destabilizing	0.38	N	0.609	neutral	None	None	None	None	N
V/Q	0.8274	likely_pathogenic	0.8049	pathogenic	-1.759	Destabilizing	0.555	D	0.613	neutral	None	None	None	None	N
V/R	0.7882	likely_pathogenic	0.7807	pathogenic	-1.096	Destabilizing	0.38	N	0.626	neutral	None	None	None	None	N
V/S	0.3009	likely_benign	0.3071	benign	-2.176	Highly Destabilizing	0.081	N	0.513	neutral	None	None	None	None	N
V/T	0.1425	likely_benign	0.1465	benign	-1.993	Destabilizing	0.001	N	0.301	neutral	None	None	None	None	N
V/W	0.9807	likely_pathogenic	0.9672	pathogenic	-1.682	Destabilizing	0.935	D	0.575	neutral	None	None	None	None	N
V/Y	0.9225	likely_pathogenic	0.908	pathogenic	-1.381	Destabilizing	0.555	D	0.625	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.