TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32596	98011;98012;98013	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
N2AB	30955	93088;93089;93090	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
N2A	30028	90307;90308;90309	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
N2B	23531	70816;70817;70818	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
Novex-1	23656	71191;71192;71193	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
Novex-2	23723	71392;71393;71394	chr2:178541291;178541290;178541289	chr2:179406018;179406017;179406016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-125
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.3417
• 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
D/Y	None	None	1.0	N	0.853	0.404	0.710160429546	gnomAD-4.0.0	1.91882E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.835E-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
D/A	0.6397	likely_pathogenic	0.7107	pathogenic	-0.247	Destabilizing	1.0	D	0.779	deleterious	N	0.513819557	None	None	I
D/C	0.9529	likely_pathogenic	0.968	pathogenic	0.031	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
D/E	0.5979	likely_pathogenic	0.664	pathogenic	-0.329	Destabilizing	0.999	D	0.56	neutral	N	0.502853201	None	None	I
D/F	0.9153	likely_pathogenic	0.933	pathogenic	-0.28	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
D/G	0.77	likely_pathogenic	0.8146	pathogenic	-0.423	Destabilizing	1.0	D	0.807	deleterious	N	0.520804244	None	None	I
D/H	0.8025	likely_pathogenic	0.8585	pathogenic	-0.081	Destabilizing	1.0	D	0.89	deleterious	N	0.475667063	None	None	I
D/I	0.8881	likely_pathogenic	0.9205	pathogenic	0.161	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
D/K	0.9166	likely_pathogenic	0.9339	pathogenic	0.282	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
D/L	0.7748	likely_pathogenic	0.8196	pathogenic	0.161	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
D/M	0.9427	likely_pathogenic	0.9583	pathogenic	0.257	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
D/N	0.4174	ambiguous	0.5002	ambiguous	0.068	Stabilizing	1.0	D	0.797	deleterious	N	0.509125813	None	None	I
D/P	0.922	likely_pathogenic	0.939	pathogenic	0.046	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
D/Q	0.8772	likely_pathogenic	0.9073	pathogenic	0.082	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
D/R	0.9244	likely_pathogenic	0.9407	pathogenic	0.44	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
D/S	0.5344	ambiguous	0.6092	pathogenic	-0.041	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
D/T	0.8193	likely_pathogenic	0.8752	pathogenic	0.09	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
D/V	0.7571	likely_pathogenic	0.8174	pathogenic	0.046	Stabilizing	1.0	D	0.819	deleterious	N	0.483616327	None	None	I
D/W	0.9807	likely_pathogenic	0.983	pathogenic	-0.184	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
D/Y	0.6086	likely_pathogenic	0.6628	pathogenic	-0.054	Destabilizing	1.0	D	0.853	deleterious	N	0.49624008	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.