TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30368	91327;91328;91329	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
N2AB	28727	86404;86405;86406	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
N2A	27800	83623;83624;83625	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
N2B	21303	64132;64133;64134	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
Novex-1	21428	64507;64508;64509	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
Novex-2	21495	64708;64709;64710	chr2:178551798;178551797;178551796	chr2:179416525;179416524;179416523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-109
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2916
• 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/R	rs1377525148	-0.219	1.0	N	0.573	0.548	0.40318662893	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
S/R	rs1377525148	-0.219	1.0	N	0.573	0.548	0.40318662893	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	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	0.1502	likely_benign	0.1746	benign	-0.357	Destabilizing	0.998	D	0.396	neutral	None	None	None	None	N
S/C	0.2405	likely_benign	0.2589	benign	-0.373	Destabilizing	1.0	D	0.693	prob.neutral	N	0.50684696	None	None	N
S/D	0.9417	likely_pathogenic	0.9349	pathogenic	0.21	Stabilizing	0.999	D	0.476	neutral	None	None	None	None	N
S/E	0.9636	likely_pathogenic	0.9642	pathogenic	0.129	Stabilizing	0.999	D	0.459	neutral	None	None	None	None	N
S/F	0.7986	likely_pathogenic	0.8352	pathogenic	-0.839	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
S/G	0.1776	likely_benign	0.1795	benign	-0.492	Destabilizing	0.999	D	0.375	neutral	N	0.512976982	None	None	N
S/H	0.8486	likely_pathogenic	0.8559	pathogenic	-0.922	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
S/I	0.8108	likely_pathogenic	0.8353	pathogenic	-0.131	Destabilizing	1.0	D	0.626	neutral	D	0.529470666	None	None	N
S/K	0.9826	likely_pathogenic	0.9857	pathogenic	-0.561	Destabilizing	0.999	D	0.466	neutral	None	None	None	None	N
S/L	0.3489	ambiguous	0.3998	ambiguous	-0.131	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	N
S/M	0.5307	ambiguous	0.578	pathogenic	-0.013	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
S/N	0.5326	ambiguous	0.529	ambiguous	-0.318	Destabilizing	0.999	D	0.459	neutral	N	0.515518641	None	None	N
S/P	0.9895	likely_pathogenic	0.9892	pathogenic	-0.176	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
S/Q	0.902	likely_pathogenic	0.9123	pathogenic	-0.528	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
S/R	0.9643	likely_pathogenic	0.973	pathogenic	-0.346	Destabilizing	1.0	D	0.573	neutral	N	0.481207834	None	None	N
S/T	0.1931	likely_benign	0.2077	benign	-0.42	Destabilizing	0.999	D	0.359	neutral	N	0.484118299	None	None	N
S/V	0.6896	likely_pathogenic	0.7295	pathogenic	-0.176	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
S/W	0.9125	likely_pathogenic	0.9208	pathogenic	-0.85	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
S/Y	0.7561	likely_pathogenic	0.7812	pathogenic	-0.579	Destabilizing	1.0	D	0.707	prob.neutral	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.