TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14433	43522;43523;43524	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
N2AB	12792	38599;38600;38601	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
N2A	11865	35818;35819;35820	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
N2B	5368	16327;16328;16329	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
Novex-1	5493	16702;16703;16704	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
Novex-2	5560	16903;16904;16905	chr2:178632709;178632708;178632707	chr2:179497436;179497435;179497434
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-95
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.3406
• 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
R/K	rs914023000	-0.488	0.997	N	0.581	0.392	0.576114100093	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
R/K	rs914023000	-0.488	0.997	N	0.581	0.392	0.576114100093	gnomAD-4.0.0	5.47495E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19701E-06	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
R/A	0.8149	likely_pathogenic	0.8704	pathogenic	-0.415	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
R/C	0.4486	ambiguous	0.4704	ambiguous	-0.404	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
R/D	0.9568	likely_pathogenic	0.9684	pathogenic	0.034	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
R/E	0.7109	likely_pathogenic	0.7769	pathogenic	0.179	Stabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
R/F	0.916	likely_pathogenic	0.9242	pathogenic	-0.163	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
R/G	0.6572	likely_pathogenic	0.7355	pathogenic	-0.74	Destabilizing	1.0	D	0.65	neutral	N	0.441796967	None	None	N
R/H	0.3123	likely_benign	0.3172	benign	-1.191	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/I	0.7407	likely_pathogenic	0.7942	pathogenic	0.457	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
R/K	0.2905	likely_benign	0.326	benign	-0.396	Destabilizing	0.997	D	0.581	neutral	N	0.507990899	None	None	N
R/L	0.6923	likely_pathogenic	0.739	pathogenic	0.457	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
R/M	0.7357	likely_pathogenic	0.7954	pathogenic	-0.083	Destabilizing	1.0	D	0.668	neutral	D	0.612499312	None	None	N
R/N	0.9268	likely_pathogenic	0.9443	pathogenic	-0.083	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
R/P	0.9804	likely_pathogenic	0.9829	pathogenic	0.189	Stabilizing	1.0	D	0.648	neutral	None	None	None	None	N
R/Q	0.2432	likely_benign	0.2774	benign	-0.108	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/S	0.8634	likely_pathogenic	0.8983	pathogenic	-0.675	Destabilizing	1.0	D	0.694	prob.neutral	N	0.507677465	None	None	N
R/T	0.7146	likely_pathogenic	0.7905	pathogenic	-0.338	Destabilizing	1.0	D	0.688	prob.neutral	N	0.501156472	None	None	N
R/V	0.784	likely_pathogenic	0.8237	pathogenic	0.189	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/W	0.5023	ambiguous	0.4919	ambiguous	0.054	Stabilizing	1.0	D	0.695	prob.neutral	D	0.612499312	None	None	N
R/Y	0.831	likely_pathogenic	0.832	pathogenic	0.365	Stabilizing	1.0	D	0.685	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.