TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22759	68500;68501;68502	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
N2AB	21118	63577;63578;63579	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
N2A	20191	60796;60797;60798	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
N2B	13694	41305;41306;41307	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
Novex-1	13819	41680;41681;41682	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
Novex-2	13886	41881;41882;41883	chr2:178578665;178578664;178578663	chr2:179443392;179443391;179443390
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-53
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1456
• 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
S/A	None	None	0.003	D	0.209	0.188	0.279776271856	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
S/A	0.0863	likely_benign	0.0814	benign	-0.336	Destabilizing	0.003	N	0.209	neutral	D	0.524298414	None	None	N
S/C	0.0888	likely_benign	0.091	benign	-0.777	Destabilizing	0.024	N	0.537	neutral	None	None	None	None	N
S/D	0.7387	likely_pathogenic	0.7713	pathogenic	-2.225	Highly Destabilizing	0.961	D	0.607	neutral	None	None	None	None	N
S/E	0.7353	likely_pathogenic	0.7517	pathogenic	-2.108	Highly Destabilizing	0.775	D	0.587	neutral	None	None	None	None	N
S/F	0.2188	likely_benign	0.2116	benign	-0.453	Destabilizing	0.961	D	0.753	deleterious	None	None	None	None	N
S/G	0.1173	likely_benign	0.1231	benign	-0.629	Destabilizing	0.633	D	0.553	neutral	None	None	None	None	N
S/H	0.415	ambiguous	0.4337	ambiguous	-1.197	Destabilizing	0.996	D	0.724	prob.delet.	None	None	None	None	N
S/I	0.2732	likely_benign	0.2531	benign	0.354	Stabilizing	0.923	D	0.757	deleterious	None	None	None	None	N
S/K	0.8639	likely_pathogenic	0.8706	pathogenic	-0.629	Destabilizing	0.775	D	0.587	neutral	None	None	None	None	N
S/L	0.1632	likely_benign	0.1466	benign	0.354	Stabilizing	0.565	D	0.68	prob.neutral	N	0.515439151	None	None	N
S/M	0.1863	likely_benign	0.171	benign	0.335	Stabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
S/N	0.2567	likely_benign	0.2757	benign	-1.335	Destabilizing	0.961	D	0.624	neutral	None	None	None	None	N
S/P	0.9823	likely_pathogenic	0.9838	pathogenic	0.158	Stabilizing	0.949	D	0.764	deleterious	D	0.522022516	None	None	N
S/Q	0.6161	likely_pathogenic	0.6035	pathogenic	-1.28	Destabilizing	0.961	D	0.665	neutral	None	None	None	None	N
S/R	0.772	likely_pathogenic	0.7927	pathogenic	-0.751	Destabilizing	0.923	D	0.776	deleterious	None	None	None	None	N
S/T	0.0918	likely_benign	0.0964	benign	-0.856	Destabilizing	0.722	D	0.557	neutral	N	0.483507797	None	None	N
S/V	0.247	likely_benign	0.2216	benign	0.158	Stabilizing	0.633	D	0.711	prob.delet.	None	None	None	None	N
S/W	0.4394	ambiguous	0.4891	ambiguous	-0.836	Destabilizing	0.996	D	0.779	deleterious	None	None	None	None	N
S/Y	0.2361	likely_benign	0.2432	benign	-0.339	Destabilizing	0.987	D	0.76	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.