TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33255	99988;99989;99990	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
N2AB	31614	95065;95066;95067	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
N2A	30687	92284;92285;92286	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
N2B	24190	72793;72794;72795	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
Novex-1	24315	73168;73169;73170	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
Novex-2	24382	73369;73370;73371	chr2:178537444;178537443;178537442	chr2:179402171;179402170;179402169
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-157
• Domain position: 53
• Structural Position: 139
• Q(SASA): 0.1437
• 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	rs1692136701	None	0.002	N	0.411	0.071	0.515259903717	gnomAD-4.0.0	7.96536E-06	None	None	None	None	N	None	0	0	None	0	2.77809E-05	None	0	0	0	0	1.21051E-04

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	0.4983	ambiguous	0.467	ambiguous	-2.065	Highly Destabilizing	0.013	N	0.312	neutral	N	0.516223222	None	None	N
V/C	0.915	likely_pathogenic	0.9062	pathogenic	-1.521	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
V/D	0.8766	likely_pathogenic	0.8586	pathogenic	-2.561	Highly Destabilizing	0.973	D	0.717	prob.delet.	N	0.48918873	None	None	N
V/E	0.7332	likely_pathogenic	0.6783	pathogenic	-2.483	Highly Destabilizing	0.887	D	0.662	neutral	None	None	None	None	N
V/F	0.4089	ambiguous	0.3964	ambiguous	-1.398	Destabilizing	0.965	D	0.661	neutral	N	0.49781082	None	None	N
V/G	0.6846	likely_pathogenic	0.6993	pathogenic	-2.464	Highly Destabilizing	0.876	D	0.657	neutral	D	0.528133727	None	None	N
V/H	0.8959	likely_pathogenic	0.8696	pathogenic	-2.03	Highly Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
V/I	0.0997	likely_benign	0.0983	benign	-1.007	Destabilizing	0.002	N	0.411	neutral	N	0.464620966	None	None	N
V/K	0.8409	likely_pathogenic	0.7918	pathogenic	-1.79	Destabilizing	0.945	D	0.663	neutral	None	None	None	None	N
V/L	0.3734	ambiguous	0.3387	benign	-1.007	Destabilizing	0.045	N	0.53	neutral	N	0.478878343	None	None	N
V/M	0.3484	ambiguous	0.3265	benign	-0.853	Destabilizing	0.963	D	0.588	neutral	None	None	None	None	N
V/N	0.7447	likely_pathogenic	0.738	pathogenic	-1.765	Destabilizing	0.717	D	0.717	prob.delet.	None	None	None	None	N
V/P	0.9905	likely_pathogenic	0.9914	pathogenic	-1.33	Destabilizing	0.837	D	0.693	prob.neutral	None	None	None	None	N
V/Q	0.7105	likely_pathogenic	0.6638	pathogenic	-1.855	Destabilizing	0.961	D	0.711	prob.delet.	None	None	None	None	N
V/R	0.787	likely_pathogenic	0.7251	pathogenic	-1.3	Destabilizing	0.973	D	0.741	deleterious	None	None	None	None	N
V/S	0.5875	likely_pathogenic	0.5884	pathogenic	-2.289	Highly Destabilizing	0.148	N	0.5	neutral	None	None	None	None	N
V/T	0.494	ambiguous	0.4623	ambiguous	-2.105	Highly Destabilizing	0.531	D	0.519	neutral	None	None	None	None	N
V/W	0.9645	likely_pathogenic	0.9582	pathogenic	-1.742	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/Y	0.8604	likely_pathogenic	0.8395	pathogenic	-1.473	Destabilizing	0.987	D	0.675	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.