TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27264	82015;82016;82017	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
N2AB	25623	77092;77093;77094	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
N2A	24696	74311;74312;74313	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
N2B	18199	54820;54821;54822	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
Novex-1	18324	55195;55196;55197	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
Novex-2	18391	55396;55397;55398	chr2:178564342;178564341;178564340	chr2:179429069;179429068;179429067
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-86
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.3392
• 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/L	None	None	0.985	N	0.404	0.205	0.45783149361	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
I/V	rs1704855362	None	0.985	N	0.355	0.183	0.537588199982	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
I/V	rs1704855362	None	0.985	N	0.355	0.183	0.537588199982	gnomAD-4.0.0	2.56236E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.13824E-05	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
I/A	0.9199	likely_pathogenic	0.891	pathogenic	-2.101	Highly Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
I/C	0.9358	likely_pathogenic	0.9184	pathogenic	-1.375	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/D	0.997	likely_pathogenic	0.9956	pathogenic	-1.727	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
I/E	0.9831	likely_pathogenic	0.9772	pathogenic	-1.542	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
I/F	0.4767	ambiguous	0.4431	ambiguous	-1.172	Destabilizing	0.999	D	0.766	deleterious	N	0.484326156	None	None	N
I/G	0.9918	likely_pathogenic	0.9877	pathogenic	-2.609	Highly Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
I/H	0.9738	likely_pathogenic	0.9664	pathogenic	-1.819	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/K	0.9503	likely_pathogenic	0.936	pathogenic	-1.47	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
I/L	0.3112	likely_benign	0.3095	benign	-0.672	Destabilizing	0.985	D	0.404	neutral	N	0.468412135	None	None	N
I/M	0.2859	likely_benign	0.2735	benign	-0.615	Destabilizing	0.999	D	0.723	deleterious	N	0.502280468	None	None	N
I/N	0.9632	likely_pathogenic	0.9498	pathogenic	-1.682	Destabilizing	0.999	D	0.857	deleterious	N	0.502280468	None	None	N
I/P	0.9965	likely_pathogenic	0.9948	pathogenic	-1.124	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
I/Q	0.9587	likely_pathogenic	0.9485	pathogenic	-1.589	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/R	0.9321	likely_pathogenic	0.9114	pathogenic	-1.165	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
I/S	0.9531	likely_pathogenic	0.9354	pathogenic	-2.448	Highly Destabilizing	0.999	D	0.831	deleterious	N	0.50101302	None	None	N
I/T	0.8581	likely_pathogenic	0.8178	pathogenic	-2.108	Highly Destabilizing	0.999	D	0.796	deleterious	N	0.486107862	None	None	N
I/V	0.0859	likely_benign	0.0789	benign	-1.124	Destabilizing	0.985	D	0.355	neutral	N	0.433531976	None	None	N
I/W	0.976	likely_pathogenic	0.9699	pathogenic	-1.416	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
I/Y	0.9152	likely_pathogenic	0.9	pathogenic	-1.118	Destabilizing	0.999	D	0.787	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.