TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33120	99583;99584;99585	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
N2AB	31479	94660;94661;94662	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
N2A	30552	91879;91880;91881	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
N2B	24055	72388;72389;72390	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
Novex-1	24180	72763;72764;72765	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
Novex-2	24247	72964;72965;72966	chr2:178537849;178537848;178537847	chr2:179402576;179402575;179402574
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-156
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1065
• 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
L/F	rs772473414	-1.615	0.338	D	0.451	0.132	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	3.91E-05	0
L/F	rs772473414	-1.615	0.338	D	0.451	0.132	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	4.41E-05	0	0
L/F	rs772473414	-1.615	0.338	D	0.451	0.132	None	gnomAD-4.0.0	1.1156E-05	None	None	None	None	N	None	2.67065E-05	0	None	0	0	None	0	0	1.35628E-05	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
L/A	0.9181	likely_pathogenic	0.9229	pathogenic	-2.599	Highly Destabilizing	0.996	D	0.745	deleterious	None	None	None	None	N
L/C	0.891	likely_pathogenic	0.9005	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.998	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/E	0.9907	likely_pathogenic	0.9895	pathogenic	-2.6	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/F	0.1523	likely_benign	0.1656	benign	-1.456	Destabilizing	0.338	N	0.451	neutral	D	0.531462034	None	None	N
L/G	0.9824	likely_pathogenic	0.9818	pathogenic	-3.219	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/H	0.9429	likely_pathogenic	0.9292	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.641222263	None	None	N
L/I	0.161	likely_benign	0.1635	benign	-0.765	Destabilizing	0.87	D	0.665	neutral	D	0.545641866	None	None	N
L/K	0.9814	likely_pathogenic	0.9792	pathogenic	-1.813	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
L/M	0.1481	likely_benign	0.1898	benign	-1.033	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
L/N	0.9874	likely_pathogenic	0.987	pathogenic	-2.324	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/P	0.9958	likely_pathogenic	0.995	pathogenic	-1.362	Destabilizing	1.0	D	0.893	deleterious	D	0.641222263	None	None	N
L/Q	0.9386	likely_pathogenic	0.9307	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/R	0.9694	likely_pathogenic	0.9609	pathogenic	-1.807	Destabilizing	1.0	D	0.861	deleterious	D	0.641222263	None	None	N
L/S	0.9806	likely_pathogenic	0.9802	pathogenic	-3.07	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/T	0.9514	likely_pathogenic	0.9547	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/V	0.2568	likely_benign	0.2689	benign	-1.362	Destabilizing	0.898	D	0.702	prob.neutral	D	0.554544486	None	None	N
L/W	0.796	likely_pathogenic	0.7434	pathogenic	-1.82	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/Y	0.788	likely_pathogenic	0.7715	pathogenic	-1.565	Destabilizing	0.998	D	0.811	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.