TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5837	17734;17735;17736	chr2:178731156;178731155;178731154	chr2:179595883;179595882;179595881
N2AB	5520	16783;16784;16785	chr2:178731156;178731155;178731154	chr2:179595883;179595882;179595881
N2A	4593	14002;14003;14004	chr2:178731156;178731155;178731154	chr2:179595883;179595882;179595881
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: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-42
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.2919
• 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
G/R	None	None	0.085	D	0.468	0.665	0.7096256102	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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
G/A	0.4907	ambiguous	0.5615	ambiguous	-0.415	Destabilizing	0.928	D	0.679	prob.neutral	D	0.590858587	None	None	N
G/C	0.6974	likely_pathogenic	0.7845	pathogenic	-0.911	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
G/D	0.4185	ambiguous	0.4923	ambiguous	-0.874	Destabilizing	0.983	D	0.775	deleterious	None	None	None	None	N
G/E	0.5295	ambiguous	0.6344	pathogenic	-1.042	Destabilizing	0.978	D	0.768	deleterious	D	0.576444736	None	None	N
G/F	0.9116	likely_pathogenic	0.9336	pathogenic	-1.222	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
G/H	0.7491	likely_pathogenic	0.7883	pathogenic	-0.625	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
G/I	0.9234	likely_pathogenic	0.9523	pathogenic	-0.574	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
G/K	0.7008	likely_pathogenic	0.7765	pathogenic	-0.802	Destabilizing	0.968	D	0.777	deleterious	None	None	None	None	N
G/L	0.8594	likely_pathogenic	0.8815	pathogenic	-0.574	Destabilizing	0.983	D	0.761	deleterious	None	None	None	None	N
G/M	0.8655	likely_pathogenic	0.9019	pathogenic	-0.407	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
G/N	0.4812	ambiguous	0.5148	ambiguous	-0.51	Destabilizing	0.983	D	0.751	deleterious	None	None	None	None	N
G/P	0.9951	likely_pathogenic	0.9968	pathogenic	-0.489	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
G/Q	0.6455	likely_pathogenic	0.7041	pathogenic	-0.864	Destabilizing	0.983	D	0.785	deleterious	None	None	None	None	N
G/R	0.6217	likely_pathogenic	0.6946	pathogenic	-0.31	Destabilizing	0.085	N	0.468	neutral	D	0.574808865	None	None	N
G/S	0.2964	likely_benign	0.3486	ambiguous	-0.631	Destabilizing	0.983	D	0.759	deleterious	None	None	None	None	N
G/T	0.5996	likely_pathogenic	0.6778	pathogenic	-0.742	Destabilizing	0.983	D	0.766	deleterious	None	None	None	None	N
G/V	0.8436	likely_pathogenic	0.8975	pathogenic	-0.489	Destabilizing	0.989	D	0.776	deleterious	D	0.623533082	None	None	N
G/W	0.8181	likely_pathogenic	0.8719	pathogenic	-1.335	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
G/Y	0.8161	likely_pathogenic	0.8556	pathogenic	-0.991	Destabilizing	0.999	D	0.795	deleterious	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.