TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8853	26782;26783;26784	chr2:178714101;178714100;178714099	chr2:179578828;179578827;179578826
N2AB	8536	25831;25832;25833	chr2:178714101;178714100;178714099	chr2:179578828;179578827;179578826
N2A	7609	23050;23051;23052	chr2:178714101;178714100;178714099	chr2:179578828;179578827;179578826
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-74
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1234
• 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	0.948	N	0.589	0.287	0.597372938306	gnomAD-4.0.0	6.84261E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99502E-07	0	0
V/L	rs757381520	-0.19	0.9	D	0.627	0.348	0.587811542155	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	4.44E-05	0
V/L	rs757381520	-0.19	0.9	D	0.627	0.348	0.587811542155	gnomAD-4.0.0	6.84261E-06	None	None	None	None	N	None	0	2.23724E-05	None	0	0	None	0	0	8.09552E-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
V/A	0.3402	ambiguous	0.4009	ambiguous	-1.654	Destabilizing	0.989	D	0.661	neutral	N	0.50324643	None	None	N
V/C	0.9402	likely_pathogenic	0.9638	pathogenic	-1.293	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/D	0.9865	likely_pathogenic	0.9916	pathogenic	-1.924	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/E	0.9602	likely_pathogenic	0.9718	pathogenic	-1.692	Destabilizing	0.999	D	0.813	deleterious	D	0.621286464	None	None	N
V/F	0.5899	likely_pathogenic	0.675	pathogenic	-0.898	Destabilizing	0.154	N	0.436	neutral	None	None	None	None	N
V/G	0.7274	likely_pathogenic	0.7936	pathogenic	-2.208	Highly Destabilizing	0.999	D	0.816	deleterious	D	0.565566947	None	None	N
V/H	0.9849	likely_pathogenic	0.9909	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
V/I	0.1058	likely_benign	0.1216	benign	-0.115	Destabilizing	0.948	D	0.589	neutral	N	0.515903509	None	None	N
V/K	0.975	likely_pathogenic	0.9824	pathogenic	-1.242	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/L	0.4937	ambiguous	0.5936	pathogenic	-0.115	Destabilizing	0.9	D	0.627	neutral	D	0.536123115	None	None	N
V/M	0.4005	ambiguous	0.5183	ambiguous	-0.307	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
V/N	0.9602	likely_pathogenic	0.9762	pathogenic	-1.591	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/P	0.9786	likely_pathogenic	0.9859	pathogenic	-0.599	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
V/Q	0.9599	likely_pathogenic	0.9717	pathogenic	-1.376	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/R	0.9536	likely_pathogenic	0.9651	pathogenic	-1.245	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/S	0.7257	likely_pathogenic	0.7996	pathogenic	-2.263	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/T	0.4702	ambiguous	0.5482	ambiguous	-1.872	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.988	likely_pathogenic	0.9935	pathogenic	-1.402	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/Y	0.9567	likely_pathogenic	0.9722	pathogenic	-0.953	Destabilizing	0.99	D	0.792	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.