TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19628	59107;59108;59109	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
N2AB	17987	54184;54185;54186	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
N2A	17060	51403;51404;51405	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
N2B	10563	31912;31913;31914	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
Novex-1	10688	32287;32288;32289	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
Novex-2	10755	32488;32489;32490	chr2:178593326;178593325;178593324	chr2:179458053;179458052;179458051
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-30
• Domain position: 50
• Structural Position: 68
• Q(SASA): 0.212
• 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/A	None	None	0.005	N	0.163	0.148	0.378674557249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	rs772550095	-0.343	0.625	N	0.507	0.221	0.413761986042	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.30736E-04	None	0	0	0
V/I	rs772550095	-0.343	0.625	N	0.507	0.221	0.413761986042	gnomAD-4.0.0	6.15913E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.0436E-04	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	0.2513	likely_benign	0.2763	benign	-1.419	Destabilizing	0.005	N	0.163	neutral	N	0.463916385	None	None	I
V/C	0.7482	likely_pathogenic	0.7785	pathogenic	-1.03	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	I
V/D	0.9601	likely_pathogenic	0.9589	pathogenic	-1.381	Destabilizing	0.966	D	0.593	neutral	N	0.51007251	None	None	I
V/E	0.9133	likely_pathogenic	0.9123	pathogenic	-1.243	Destabilizing	0.842	D	0.546	neutral	None	None	None	None	I
V/F	0.704	likely_pathogenic	0.6737	pathogenic	-0.831	Destabilizing	0.966	D	0.535	neutral	N	0.479558311	None	None	I
V/G	0.5863	likely_pathogenic	0.6159	pathogenic	-1.854	Destabilizing	0.669	D	0.575	neutral	N	0.492386329	None	None	I
V/H	0.9693	likely_pathogenic	0.969	pathogenic	-1.431	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	I
V/I	0.1284	likely_benign	0.1186	benign	-0.267	Destabilizing	0.625	D	0.507	neutral	N	0.467152049	None	None	I
V/K	0.9605	likely_pathogenic	0.9604	pathogenic	-1.225	Destabilizing	0.842	D	0.541	neutral	None	None	None	None	I
V/L	0.595	likely_pathogenic	0.5639	ambiguous	-0.267	Destabilizing	0.625	D	0.448	neutral	N	0.47122636	None	None	I
V/M	0.5258	ambiguous	0.4762	ambiguous	-0.342	Destabilizing	0.991	D	0.484	neutral	None	None	None	None	I
V/N	0.8683	likely_pathogenic	0.8749	pathogenic	-1.363	Destabilizing	0.974	D	0.602	neutral	None	None	None	None	I
V/P	0.9302	likely_pathogenic	0.9373	pathogenic	-0.618	Destabilizing	0.974	D	0.585	neutral	None	None	None	None	I
V/Q	0.9062	likely_pathogenic	0.9137	pathogenic	-1.284	Destabilizing	0.974	D	0.601	neutral	None	None	None	None	I
V/R	0.9422	likely_pathogenic	0.9448	pathogenic	-1.014	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	I
V/S	0.5638	ambiguous	0.5992	pathogenic	-1.946	Destabilizing	0.728	D	0.544	neutral	None	None	None	None	I
V/T	0.509	ambiguous	0.5304	ambiguous	-1.664	Destabilizing	0.029	N	0.161	neutral	None	None	None	None	I
V/W	0.9912	likely_pathogenic	0.9902	pathogenic	-1.188	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	I
V/Y	0.9408	likely_pathogenic	0.94	pathogenic	-0.785	Destabilizing	0.991	D	0.545	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.