TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14100	42523;42524;42525	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
N2AB	12459	37600;37601;37602	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
N2A	11532	34819;34820;34821	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
N2B	5035	15328;15329;15330	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
Novex-1	5160	15703;15704;15705	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
Novex-2	5227	15904;15905;15906	chr2:178634483;178634482;178634481	chr2:179499210;179499209;179499208
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: Ig-91
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.2985
• 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	rs1228652507	-1.04	0.953	N	0.329	0.158	0.636416215821	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	rs1228652507	-1.04	0.953	N	0.329	0.158	0.636416215821	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43336E-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	0.7302	likely_pathogenic	0.7675	pathogenic	-2.047	Highly Destabilizing	0.985	D	0.54	neutral	None	None	None	None	N
I/C	0.8843	likely_pathogenic	0.9072	pathogenic	-1.281	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
I/D	0.9492	likely_pathogenic	0.9421	pathogenic	-1.579	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
I/E	0.8871	likely_pathogenic	0.8666	pathogenic	-1.459	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
I/F	0.4129	ambiguous	0.3794	ambiguous	-1.244	Destabilizing	0.135	N	0.254	neutral	D	0.541084893	None	None	N
I/G	0.9373	likely_pathogenic	0.9461	pathogenic	-2.497	Highly Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
I/H	0.869	likely_pathogenic	0.8475	pathogenic	-1.708	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
I/K	0.7768	likely_pathogenic	0.734	pathogenic	-1.445	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
I/L	0.2248	likely_benign	0.2223	benign	-0.818	Destabilizing	0.817	D	0.317	neutral	N	0.510594613	None	None	N
I/M	0.1582	likely_benign	0.1556	benign	-0.671	Destabilizing	0.999	D	0.561	neutral	N	0.51544648	None	None	N
I/N	0.6714	likely_pathogenic	0.6429	pathogenic	-1.48	Destabilizing	0.997	D	0.689	prob.neutral	D	0.729268122	None	None	N
I/P	0.9782	likely_pathogenic	0.9777	pathogenic	-1.201	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
I/Q	0.8103	likely_pathogenic	0.7784	pathogenic	-1.493	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
I/R	0.6992	likely_pathogenic	0.6639	pathogenic	-1.002	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
I/S	0.6855	likely_pathogenic	0.7104	pathogenic	-2.203	Highly Destabilizing	0.961	D	0.601	neutral	D	0.667029826	None	None	N
I/T	0.4395	ambiguous	0.4831	ambiguous	-1.944	Destabilizing	0.4	N	0.284	neutral	D	0.609982464	None	None	N
I/V	0.1166	likely_benign	0.1365	benign	-1.201	Destabilizing	0.953	D	0.329	neutral	N	0.495272043	None	None	N
I/W	0.9426	likely_pathogenic	0.9415	pathogenic	-1.443	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
I/Y	0.7892	likely_pathogenic	0.779	pathogenic	-1.175	Destabilizing	0.991	D	0.584	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.