TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33213	99862;99863;99864	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
N2AB	31572	94939;94940;94941	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
N2A	30645	92158;92159;92160	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
N2B	24148	72667;72668;72669	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
Novex-1	24273	73042;73043;73044	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
Novex-2	24340	73243;73244;73245	chr2:178537570;178537569;178537568	chr2:179402297;179402296;179402295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-157
• Domain position: 11
• Structural Position: 26
• Q(SASA): 0.3235
• 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
T/I	None	None	0.998	N	0.501	0.384	0.400033932507	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
T/A	0.1464	likely_benign	0.144	benign	-0.559	Destabilizing	0.461	N	0.42	neutral	N	0.483088431	None	None	N
T/C	0.6713	likely_pathogenic	0.7278	pathogenic	-0.387	Destabilizing	1.0	D	0.559	neutral	None	None	None	None	N
T/D	0.682	likely_pathogenic	0.632	pathogenic	0.29	Stabilizing	0.944	D	0.493	neutral	None	None	None	None	N
T/E	0.6673	likely_pathogenic	0.6079	pathogenic	0.251	Stabilizing	0.983	D	0.498	neutral	None	None	None	None	N
T/F	0.5182	ambiguous	0.504	ambiguous	-0.871	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
T/G	0.5289	ambiguous	0.5679	pathogenic	-0.748	Destabilizing	0.993	D	0.526	neutral	None	None	None	None	N
T/H	0.5232	ambiguous	0.5101	ambiguous	-0.981	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
T/I	0.3499	ambiguous	0.2983	benign	-0.17	Destabilizing	0.998	D	0.501	neutral	N	0.513411338	None	None	N
T/K	0.622	likely_pathogenic	0.5766	pathogenic	-0.452	Destabilizing	0.983	D	0.492	neutral	N	0.466406825	None	None	N
T/L	0.1976	likely_benign	0.1827	benign	-0.17	Destabilizing	0.994	D	0.491	neutral	None	None	None	None	N
T/M	0.1523	likely_benign	0.1497	benign	-0.013	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	N
T/N	0.2249	likely_benign	0.2064	benign	-0.325	Destabilizing	0.944	D	0.448	neutral	None	None	None	None	N
T/P	0.2301	likely_benign	0.205	benign	-0.268	Destabilizing	0.989	D	0.497	neutral	N	0.493091994	None	None	N
T/Q	0.4954	ambiguous	0.4704	ambiguous	-0.496	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	N
T/R	0.5407	ambiguous	0.51	ambiguous	-0.206	Destabilizing	0.999	D	0.527	neutral	N	0.482915073	None	None	N
T/S	0.1476	likely_benign	0.161	benign	-0.613	Destabilizing	0.063	N	0.208	neutral	N	0.413687061	None	None	N
T/V	0.237	likely_benign	0.2068	benign	-0.268	Destabilizing	0.991	D	0.43	neutral	None	None	None	None	N
T/W	0.8825	likely_pathogenic	0.8766	pathogenic	-0.832	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/Y	0.5781	likely_pathogenic	0.5624	ambiguous	-0.57	Destabilizing	1.0	D	0.604	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.