TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9160	27703;27704;27705	chr2:178712444;178712443;178712442	chr2:179577171;179577170;179577169
N2AB	8843	26752;26753;26754	chr2:178712444;178712443;178712442	chr2:179577171;179577170;179577169
N2A	7916	23971;23972;23973	chr2:178712444;178712443;178712442	chr2:179577171;179577170;179577169
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-77
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2517
• 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
I/T	rs2076799987	None	0.006	D	0.347	0.362	0.733868726719	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs2076799987	None	0.006	D	0.347	0.362	0.733868726719	gnomAD-4.0.0	6.57445E-06	None	None	None	None	I	None	2.41476E-05	0	None	0	0	None	0	0	0	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
I/A	0.5165	ambiguous	0.4233	ambiguous	-2.209	Highly Destabilizing	0.207	N	0.464	neutral	None	None	None	None	I
I/C	0.7214	likely_pathogenic	0.6411	pathogenic	-1.388	Destabilizing	0.981	D	0.564	neutral	None	None	None	None	I
I/D	0.8819	likely_pathogenic	0.8559	pathogenic	-1.969	Destabilizing	0.818	D	0.617	neutral	None	None	None	None	I
I/E	0.7431	likely_pathogenic	0.6813	pathogenic	-1.88	Destabilizing	0.818	D	0.625	neutral	None	None	None	None	I
I/F	0.1548	likely_benign	0.1397	benign	-1.521	Destabilizing	0.527	D	0.487	neutral	None	None	None	None	I
I/G	0.8129	likely_pathogenic	0.7421	pathogenic	-2.642	Highly Destabilizing	0.818	D	0.617	neutral	None	None	None	None	I
I/H	0.6324	likely_pathogenic	0.5785	pathogenic	-1.98	Destabilizing	0.981	D	0.645	neutral	None	None	None	None	I
I/K	0.5307	ambiguous	0.4687	ambiguous	-1.582	Destabilizing	0.627	D	0.625	neutral	N	0.513893258	None	None	I
I/L	0.1183	likely_benign	0.1013	benign	-1.03	Destabilizing	0.001	N	0.145	neutral	N	0.503448713	None	None	I
I/M	0.105	likely_benign	0.0944	benign	-0.778	Destabilizing	0.627	D	0.506	neutral	N	0.50539294	None	None	I
I/N	0.481	ambiguous	0.4224	ambiguous	-1.529	Destabilizing	0.818	D	0.631	neutral	None	None	None	None	I
I/P	0.9037	likely_pathogenic	0.8734	pathogenic	-1.396	Destabilizing	0.932	D	0.629	neutral	None	None	None	None	I
I/Q	0.5752	likely_pathogenic	0.5081	ambiguous	-1.604	Destabilizing	0.932	D	0.639	neutral	None	None	None	None	I
I/R	0.4214	ambiguous	0.3704	ambiguous	-1.081	Destabilizing	0.773	D	0.633	neutral	D	0.530275993	None	None	I
I/S	0.5002	ambiguous	0.4244	ambiguous	-2.198	Highly Destabilizing	0.241	N	0.568	neutral	None	None	None	None	I
I/T	0.3629	ambiguous	0.2836	benign	-1.977	Destabilizing	0.006	N	0.347	neutral	D	0.525018851	None	None	I
I/V	0.0844	likely_benign	0.0752	benign	-1.396	Destabilizing	0.006	N	0.17	neutral	N	0.491170062	None	None	I
I/W	0.7159	likely_pathogenic	0.6823	pathogenic	-1.734	Destabilizing	0.981	D	0.697	prob.neutral	None	None	None	None	I
I/Y	0.4972	ambiguous	0.4509	ambiguous	-1.485	Destabilizing	0.818	D	0.565	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.