TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1094	3505;3506;3507	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
N2AB	1094	3505;3506;3507	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
N2A	1094	3505;3506;3507	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
N2B	1048	3367;3368;3369	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
Novex-1	1048	3367;3368;3369	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
Novex-2	1048	3367;3368;3369	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037
Novex-3	1094	3505;3506;3507	chr2:178782312;178782311;178782310	chr2:179647039;179647038;179647037

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-4
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7106
• 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
V/L	None	None	0.034	N	0.477	0.088	0.214338557667	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.1699	likely_benign	0.1672	benign	-0.512	Destabilizing	0.201	N	0.567	neutral	N	0.442493228	None	None	I
V/C	0.8472	likely_pathogenic	0.8416	pathogenic	-0.726	Destabilizing	0.982	D	0.567	neutral	None	None	None	None	I
V/D	0.4084	ambiguous	0.373	ambiguous	-0.165	Destabilizing	0.826	D	0.66	neutral	None	None	None	None	I
V/E	0.2346	likely_benign	0.2143	benign	-0.269	Destabilizing	0.781	D	0.631	neutral	N	0.465444582	None	None	I
V/F	0.2081	likely_benign	0.1987	benign	-0.667	Destabilizing	0.7	D	0.545	neutral	None	None	None	None	I
V/G	0.2675	likely_benign	0.2504	benign	-0.655	Destabilizing	0.638	D	0.653	neutral	N	0.500082925	None	None	I
V/H	0.5843	likely_pathogenic	0.5746	pathogenic	-0.212	Destabilizing	0.982	D	0.674	neutral	None	None	None	None	I
V/I	0.0872	likely_benign	0.0838	benign	-0.28	Destabilizing	0.002	N	0.318	neutral	None	None	None	None	I
V/K	0.3059	likely_benign	0.2991	benign	-0.46	Destabilizing	0.7	D	0.627	neutral	None	None	None	None	I
V/L	0.1659	likely_benign	0.1634	benign	-0.28	Destabilizing	0.034	N	0.477	neutral	N	0.4559612	None	None	I
V/M	0.1295	likely_benign	0.1214	benign	-0.385	Destabilizing	0.034	N	0.495	neutral	N	0.483303749	None	None	I
V/N	0.3212	likely_benign	0.2969	benign	-0.235	Destabilizing	0.826	D	0.659	neutral	None	None	None	None	I
V/P	0.7291	likely_pathogenic	0.7238	pathogenic	-0.322	Destabilizing	0.935	D	0.623	neutral	None	None	None	None	I
V/Q	0.2693	likely_benign	0.2586	benign	-0.455	Destabilizing	0.7	D	0.626	neutral	None	None	None	None	I
V/R	0.2738	likely_benign	0.2749	benign	0.029	Stabilizing	0.7	D	0.663	neutral	None	None	None	None	I
V/S	0.2105	likely_benign	0.204	benign	-0.634	Destabilizing	0.7	D	0.596	neutral	None	None	None	None	I
V/T	0.1564	likely_benign	0.1553	benign	-0.631	Destabilizing	0.399	N	0.547	neutral	None	None	None	None	I
V/W	0.8189	likely_pathogenic	0.8061	pathogenic	-0.741	Destabilizing	0.982	D	0.699	prob.neutral	None	None	None	None	I
V/Y	0.626	likely_pathogenic	0.6142	pathogenic	-0.445	Destabilizing	0.826	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.