TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15373	46342;46343;46344	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
N2AB	13732	41419;41420;41421	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
N2A	12805	38638;38639;38640	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
N2B	6308	19147;19148;19149	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
Novex-1	6433	19522;19523;19524	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
Novex-2	6500	19723;19724;19725	chr2:178620404;178620403;178620402	chr2:179485131;179485130;179485129
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-105
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.11
• 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/D	rs2058089139	None	0.998	D	0.853	0.483	0.75824790645	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
V/D	rs2058089139	None	0.998	D	0.853	0.483	0.75824790645	gnomAD-4.0.0	6.58302E-06	None	None	None	None	N	None	0	6.56858E-05	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
V/A	0.4952	ambiguous	0.4865	ambiguous	-1.846	Destabilizing	0.333	N	0.4	neutral	N	0.455867241	None	None	N
V/C	0.8579	likely_pathogenic	0.8774	pathogenic	-1.293	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/D	0.9956	likely_pathogenic	0.994	pathogenic	-2.379	Highly Destabilizing	0.998	D	0.853	deleterious	D	0.554560137	None	None	N
V/E	0.9893	likely_pathogenic	0.9874	pathogenic	-2.125	Highly Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
V/F	0.6846	likely_pathogenic	0.7223	pathogenic	-0.985	Destabilizing	0.999	D	0.719	prob.delet.	N	0.450486839	None	None	N
V/G	0.7842	likely_pathogenic	0.7717	pathogenic	-2.415	Highly Destabilizing	0.989	D	0.806	deleterious	D	0.55438433	None	None	N
V/H	0.9953	likely_pathogenic	0.9955	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/I	0.1474	likely_benign	0.1535	benign	-0.243	Destabilizing	0.987	D	0.53	neutral	N	0.448682939	None	None	N
V/K	0.9918	likely_pathogenic	0.9905	pathogenic	-1.321	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/L	0.4433	ambiguous	0.5114	ambiguous	-0.243	Destabilizing	0.973	D	0.635	neutral	N	0.461603962	None	None	N
V/M	0.5639	ambiguous	0.6112	pathogenic	-0.393	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
V/N	0.9845	likely_pathogenic	0.9793	pathogenic	-1.728	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/P	0.9881	likely_pathogenic	0.9897	pathogenic	-0.751	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
V/Q	0.9822	likely_pathogenic	0.9808	pathogenic	-1.492	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/R	0.9806	likely_pathogenic	0.9779	pathogenic	-1.348	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
V/S	0.904	likely_pathogenic	0.8831	pathogenic	-2.353	Highly Destabilizing	0.983	D	0.79	deleterious	None	None	None	None	N
V/T	0.7803	likely_pathogenic	0.7697	pathogenic	-1.948	Destabilizing	0.992	D	0.657	neutral	None	None	None	None	N
V/W	0.9971	likely_pathogenic	0.9978	pathogenic	-1.543	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/Y	0.9793	likely_pathogenic	0.9802	pathogenic	-1.118	Destabilizing	1.0	D	0.719	prob.delet.	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.