TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30379	91360;91361;91362	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
N2AB	28738	86437;86438;86439	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
N2A	27811	83656;83657;83658	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
N2B	21314	64165;64166;64167	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
Novex-1	21439	64540;64541;64542	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
Novex-2	21506	64741;64742;64743	chr2:178551765;178551764;178551763	chr2:179416492;179416491;179416490
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: Fn3-109
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0898
• 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
I/V	rs746319162	-1.2	0.026	N	0.243	0.078	0.265010934533	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs746319162	-1.2	0.026	N	0.243	0.078	0.265010934533	gnomAD-4.0.0	4.7735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71621E-06	1.43279E-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
I/A	0.4733	ambiguous	0.5368	ambiguous	-2.03	Highly Destabilizing	0.851	D	0.557	neutral	None	None	None	None	N
I/C	0.6592	likely_pathogenic	0.7169	pathogenic	-1.133	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
I/D	0.9465	likely_pathogenic	0.9577	pathogenic	-2.059	Highly Destabilizing	0.996	D	0.796	deleterious	None	None	None	None	N
I/E	0.9085	likely_pathogenic	0.9248	pathogenic	-1.821	Destabilizing	0.988	D	0.771	deleterious	None	None	None	None	N
I/F	0.3159	likely_benign	0.3801	ambiguous	-1.171	Destabilizing	0.968	D	0.687	prob.neutral	D	0.523020617	None	None	N
I/G	0.8246	likely_pathogenic	0.8566	pathogenic	-2.58	Highly Destabilizing	0.988	D	0.767	deleterious	None	None	None	None	N
I/H	0.8263	likely_pathogenic	0.8592	pathogenic	-2.14	Highly Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
I/K	0.8253	likely_pathogenic	0.8516	pathogenic	-1.222	Destabilizing	0.988	D	0.772	deleterious	None	None	None	None	N
I/L	0.1188	likely_benign	0.1309	benign	-0.445	Destabilizing	0.011	N	0.267	neutral	N	0.462510876	None	None	N
I/M	0.1762	likely_benign	0.1974	benign	-0.389	Destabilizing	0.968	D	0.697	prob.neutral	N	0.48706673	None	None	N
I/N	0.6248	likely_pathogenic	0.6704	pathogenic	-1.548	Destabilizing	0.995	D	0.806	deleterious	N	0.461868449	None	None	N
I/P	0.9183	likely_pathogenic	0.9428	pathogenic	-0.953	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
I/Q	0.7885	likely_pathogenic	0.8235	pathogenic	-1.369	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
I/R	0.7474	likely_pathogenic	0.7882	pathogenic	-1.154	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
I/S	0.5512	ambiguous	0.6062	pathogenic	-2.264	Highly Destabilizing	0.984	D	0.696	prob.neutral	N	0.5025652	None	None	N
I/T	0.4822	ambiguous	0.5272	ambiguous	-1.872	Destabilizing	0.896	D	0.661	neutral	N	0.488691826	None	None	N
I/V	0.0645	likely_benign	0.065	benign	-0.953	Destabilizing	0.026	N	0.243	neutral	N	0.435977635	None	None	N
I/W	0.9464	likely_pathogenic	0.9592	pathogenic	-1.568	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
I/Y	0.7925	likely_pathogenic	0.8293	pathogenic	-1.2	Destabilizing	0.996	D	0.747	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.