TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33225	99898;99899;99900	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
N2AB	31584	94975;94976;94977	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
N2A	30657	92194;92195;92196	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
N2B	24160	72703;72704;72705	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
Novex-1	24285	73078;73079;73080	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
Novex-2	24352	73279;73280;73281	chr2:178537534;178537533;178537532	chr2:179402261;179402260;179402259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-157
• Domain position: 23
• Structural Position: 43
• Q(SASA): 0.2738
• 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/I	None	None	None	N	0.175	0.097	0.363356657567	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31884E-05	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	0.2155	likely_benign	0.2207	benign	-1.368	Destabilizing	0.239	N	0.344	neutral	N	0.421176833	None	None	N
V/C	0.8534	likely_pathogenic	0.8681	pathogenic	-0.724	Destabilizing	0.988	D	0.454	neutral	None	None	None	None	N
V/D	0.4811	ambiguous	0.524	ambiguous	-1.244	Destabilizing	0.946	D	0.615	neutral	None	None	None	None	N
V/E	0.3237	likely_benign	0.3289	benign	-1.271	Destabilizing	0.868	D	0.581	neutral	N	0.406418025	None	None	N
V/F	0.2597	likely_benign	0.2785	benign	-1.141	Destabilizing	0.868	D	0.428	neutral	None	None	None	None	N
V/G	0.4361	ambiguous	0.4573	ambiguous	-1.65	Destabilizing	0.947	D	0.596	neutral	N	0.486863108	None	None	N
V/H	0.6819	likely_pathogenic	0.6982	pathogenic	-1.238	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
V/I	0.0814	likely_benign	0.0887	benign	-0.703	Destabilizing	None	N	0.175	neutral	N	0.425257288	None	None	N
V/K	0.3843	ambiguous	0.3628	ambiguous	-1.202	Destabilizing	0.861	D	0.569	neutral	None	None	None	None	N
V/L	0.1992	likely_benign	0.2089	benign	-0.703	Destabilizing	0.004	N	0.234	neutral	N	0.443149616	None	None	N
V/M	0.1499	likely_benign	0.1633	benign	-0.463	Destabilizing	0.107	N	0.291	neutral	None	None	None	None	N
V/N	0.3527	ambiguous	0.3771	ambiguous	-0.879	Destabilizing	0.738	D	0.627	neutral	None	None	None	None	N
V/P	0.5351	ambiguous	0.5012	ambiguous	-0.89	Destabilizing	0.738	D	0.595	neutral	None	None	None	None	N
V/Q	0.3538	ambiguous	0.3424	ambiguous	-1.08	Destabilizing	0.815	D	0.603	neutral	None	None	None	None	N
V/R	0.3877	ambiguous	0.3672	ambiguous	-0.637	Destabilizing	0.93	D	0.623	neutral	None	None	None	None	N
V/S	0.2699	likely_benign	0.2753	benign	-1.315	Destabilizing	0.878	D	0.529	neutral	None	None	None	None	N
V/T	0.2387	likely_benign	0.2513	benign	-1.243	Destabilizing	0.289	N	0.357	neutral	None	None	None	None	N
V/W	0.9237	likely_pathogenic	0.9328	pathogenic	-1.323	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
V/Y	0.7079	likely_pathogenic	0.7166	pathogenic	-1.051	Destabilizing	0.93	D	0.423	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.