TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25214	75865;75866;75867	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
N2AB	23573	70942;70943;70944	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
N2A	22646	68161;68162;68163	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
N2B	16149	48670;48671;48672	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
Novex-1	16274	49045;49046;49047	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
Novex-2	16341	49246;49247;49248	chr2:178570492;178570491;178570490	chr2:179435219;179435218;179435217
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: Fn3-71
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.1939
• 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/T	rs1241605082	-1.858	0.124	N	0.637	0.21	0.687524581047	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66445E-04
I/T	rs1241605082	-1.858	0.124	N	0.637	0.21	0.687524581047	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02718E-05

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	0.4973	ambiguous	0.5279	ambiguous	-1.724	Destabilizing	0.005	N	0.329	neutral	None	None	None	None	N
I/C	0.6405	likely_pathogenic	0.7048	pathogenic	-1.217	Destabilizing	0.909	D	0.691	prob.neutral	None	None	None	None	N
I/D	0.9406	likely_pathogenic	0.9482	pathogenic	-0.779	Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
I/E	0.9001	likely_pathogenic	0.9112	pathogenic	-0.711	Destabilizing	0.726	D	0.807	deleterious	None	None	None	None	N
I/F	0.1554	likely_benign	0.1786	benign	-1.04	Destabilizing	0.497	N	0.603	neutral	N	0.488561327	None	None	N
I/G	0.8316	likely_pathogenic	0.8555	pathogenic	-2.118	Highly Destabilizing	0.567	D	0.77	deleterious	None	None	None	None	N
I/H	0.78	likely_pathogenic	0.8263	pathogenic	-1.294	Destabilizing	0.968	D	0.811	deleterious	None	None	None	None	N
I/K	0.779	likely_pathogenic	0.8085	pathogenic	-1.159	Destabilizing	0.726	D	0.807	deleterious	None	None	None	None	N
I/L	0.1471	likely_benign	0.1515	benign	-0.69	Destabilizing	0.025	N	0.428	neutral	N	0.496084732	None	None	N
I/M	0.1746	likely_benign	0.1769	benign	-0.66	Destabilizing	0.497	N	0.577	neutral	N	0.481879397	None	None	N
I/N	0.6575	likely_pathogenic	0.6868	pathogenic	-1.073	Destabilizing	0.859	D	0.84	deleterious	N	0.505517061	None	None	N
I/P	0.741	likely_pathogenic	0.7748	pathogenic	-1.004	Destabilizing	0.726	D	0.825	deleterious	None	None	None	None	N
I/Q	0.7882	likely_pathogenic	0.8248	pathogenic	-1.113	Destabilizing	0.89	D	0.831	deleterious	None	None	None	None	N
I/R	0.6895	likely_pathogenic	0.7307	pathogenic	-0.726	Destabilizing	0.726	D	0.841	deleterious	None	None	None	None	N
I/S	0.5561	ambiguous	0.5972	pathogenic	-1.818	Destabilizing	0.124	N	0.729	prob.delet.	N	0.486652337	None	None	N
I/T	0.4375	ambiguous	0.4749	ambiguous	-1.608	Destabilizing	0.124	N	0.637	neutral	N	0.475549521	None	None	N
I/V	0.0737	likely_benign	0.074	benign	-1.004	Destabilizing	None	N	0.19	neutral	N	0.392050713	None	None	N
I/W	0.8471	likely_pathogenic	0.878	pathogenic	-1.127	Destabilizing	0.968	D	0.809	deleterious	None	None	None	None	N
I/Y	0.6029	likely_pathogenic	0.675	pathogenic	-0.896	Destabilizing	0.726	D	0.712	prob.delet.	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.