TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27325	82198;82199;82200	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
N2AB	25684	77275;77276;77277	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
N2A	24757	74494;74495;74496	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
N2B	18260	55003;55004;55005	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
Novex-1	18385	55378;55379;55380	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
Novex-2	18452	55579;55580;55581	chr2:178564159;178564158;178564157	chr2:179428886;179428885;179428884
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: Ig-140
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.1895
• 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/N	None	None	0.999	D	0.823	0.639	0.853896731775	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85835E-06	0	0
I/T	rs1226922213	-2.21	0.989	N	0.643	0.595	0.816803860896	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-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	0.6943	likely_pathogenic	0.7623	pathogenic	-2.214	Highly Destabilizing	0.992	D	0.522	neutral	None	None	None	None	N
I/C	0.777	likely_pathogenic	0.8174	pathogenic	-1.489	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
I/D	0.9333	likely_pathogenic	0.9516	pathogenic	-1.749	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
I/E	0.7783	likely_pathogenic	0.8257	pathogenic	-1.648	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
I/F	0.2205	likely_benign	0.2658	benign	-1.402	Destabilizing	0.998	D	0.619	neutral	N	0.49163472	None	None	N
I/G	0.8564	likely_pathogenic	0.8954	pathogenic	-2.659	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
I/H	0.7357	likely_pathogenic	0.793	pathogenic	-1.909	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
I/K	0.4992	ambiguous	0.5785	pathogenic	-1.597	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
I/L	0.1756	likely_benign	0.2025	benign	-0.998	Destabilizing	0.889	D	0.401	neutral	N	0.487378304	None	None	N
I/M	0.1078	likely_benign	0.1218	benign	-0.852	Destabilizing	0.998	D	0.641	neutral	D	0.536907926	None	None	N
I/N	0.5499	ambiguous	0.6295	pathogenic	-1.531	Destabilizing	0.999	D	0.823	deleterious	D	0.527642647	None	None	N
I/P	0.9624	likely_pathogenic	0.9708	pathogenic	-1.376	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
I/Q	0.6117	likely_pathogenic	0.6899	pathogenic	-1.584	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/R	0.4189	ambiguous	0.5049	ambiguous	-1.121	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/S	0.6534	likely_pathogenic	0.7255	pathogenic	-2.26	Highly Destabilizing	0.998	D	0.709	prob.delet.	N	0.517665467	None	None	N
I/T	0.5761	likely_pathogenic	0.6561	pathogenic	-2.023	Highly Destabilizing	0.989	D	0.643	neutral	N	0.506954271	None	None	N
I/V	0.1102	likely_benign	0.1297	benign	-1.376	Destabilizing	0.333	N	0.221	neutral	N	0.510025182	None	None	N
I/W	0.7581	likely_pathogenic	0.7955	pathogenic	-1.566	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
I/Y	0.5774	likely_pathogenic	0.637	pathogenic	-1.342	Destabilizing	1.0	D	0.734	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.