TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19216	57871;57872;57873	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
N2AB	17575	52948;52949;52950	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
N2A	16648	50167;50168;50169	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
N2B	10151	30676;30677;30678	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
Novex-1	10276	31051;31052;31053	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
Novex-2	10343	31252;31253;31254	chr2:178595708;178595707;178595706	chr2:179460435;179460434;179460433
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-27
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2117
• 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
I/V	rs374058726	-1.529	0.006	N	0.24	0.056	None	gnomAD-2.1.1	3.64789E-04	None	None	None	None	I	None	8.52E-05	1.62112E-03	None	0	0	None	0	None	0	2.74079E-04	1.0043E-03
I/V	rs374058726	-1.529	0.006	N	0.24	0.056	None	gnomAD-3.1.2	2.56501E-04	None	None	None	None	I	None	9.66E-05	6.5505E-04	0	0	0	None	0	0	3.38285E-04	0	9.56938E-04
I/V	rs374058726	-1.529	0.006	N	0.24	0.056	None	gnomAD-4.0.0	3.20132E-04	None	None	None	None	I	None	6.68199E-05	1.41257E-03	None	0	0	None	1.56794E-05	0	3.47289E-04	2.22936E-05	2.24661E-04

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
I/A	0.9651	likely_pathogenic	0.9762	pathogenic	-2.328	Highly Destabilizing	0.754	D	0.691	prob.neutral	None	None	None	None	I
I/C	0.9664	likely_pathogenic	0.9775	pathogenic	-1.579	Destabilizing	0.994	D	0.747	deleterious	None	None	None	None	I
I/D	0.9989	likely_pathogenic	0.9992	pathogenic	-2.413	Highly Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	I
I/E	0.9956	likely_pathogenic	0.9969	pathogenic	-2.342	Highly Destabilizing	0.978	D	0.84	deleterious	None	None	None	None	I
I/F	0.9441	likely_pathogenic	0.9582	pathogenic	-1.69	Destabilizing	0.942	D	0.757	deleterious	N	0.515320111	None	None	I
I/G	0.9964	likely_pathogenic	0.9974	pathogenic	-2.735	Highly Destabilizing	0.978	D	0.835	deleterious	None	None	None	None	I
I/H	0.9968	likely_pathogenic	0.9977	pathogenic	-2.043	Highly Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	I
I/K	0.9916	likely_pathogenic	0.9938	pathogenic	-1.702	Destabilizing	0.978	D	0.839	deleterious	None	None	None	None	I
I/L	0.402	ambiguous	0.4403	ambiguous	-1.219	Destabilizing	0.294	N	0.471	neutral	D	0.526893215	None	None	I
I/M	0.5845	likely_pathogenic	0.634	pathogenic	-0.919	Destabilizing	0.942	D	0.728	prob.delet.	D	0.524602956	None	None	I
I/N	0.9815	likely_pathogenic	0.9862	pathogenic	-1.692	Destabilizing	0.99	D	0.843	deleterious	D	0.536973219	None	None	I
I/P	0.9636	likely_pathogenic	0.98	pathogenic	-1.563	Destabilizing	0.993	D	0.847	deleterious	None	None	None	None	I
I/Q	0.9928	likely_pathogenic	0.9948	pathogenic	-1.821	Destabilizing	0.993	D	0.839	deleterious	None	None	None	None	I
I/R	0.9884	likely_pathogenic	0.9922	pathogenic	-1.114	Destabilizing	0.978	D	0.842	deleterious	None	None	None	None	I
I/S	0.9811	likely_pathogenic	0.9862	pathogenic	-2.325	Highly Destabilizing	0.942	D	0.806	deleterious	D	0.524856445	None	None	I
I/T	0.9466	likely_pathogenic	0.9601	pathogenic	-2.133	Highly Destabilizing	0.822	D	0.784	deleterious	N	0.501979251	None	None	I
I/V	0.077	likely_benign	0.0852	benign	-1.563	Destabilizing	0.006	N	0.24	neutral	N	0.499629256	None	None	I
I/W	0.9985	likely_pathogenic	0.999	pathogenic	-1.909	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	I
I/Y	0.993	likely_pathogenic	0.9951	pathogenic	-1.677	Destabilizing	0.978	D	0.779	deleterious	None	None	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.