TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14532	43819;43820;43821	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
N2AB	12891	38896;38897;38898	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
N2A	11964	36115;36116;36117	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
N2B	5467	16624;16625;16626	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
Novex-1	5592	16999;17000;17001	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
Novex-2	5659	17200;17201;17202	chr2:178632300;178632299;178632298	chr2:179497027;179497026;179497025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-96
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.4134
• 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
N/H	None	None	1.0	D	0.529	0.743	0.599259136914	gnomAD-4.0.0	3.20359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74713E-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
N/A	0.8187	likely_pathogenic	0.752	pathogenic	-0.417	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
N/C	0.895	likely_pathogenic	0.8694	pathogenic	0.377	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
N/D	0.3104	likely_benign	0.2056	benign	-0.196	Destabilizing	0.999	D	0.537	neutral	D	0.5450119	None	None	N
N/E	0.8246	likely_pathogenic	0.7629	pathogenic	-0.229	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
N/F	0.9621	likely_pathogenic	0.9523	pathogenic	-0.736	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
N/G	0.5984	likely_pathogenic	0.5145	ambiguous	-0.604	Destabilizing	0.999	D	0.506	neutral	None	None	None	None	N
N/H	0.5112	ambiguous	0.4714	ambiguous	-0.695	Destabilizing	1.0	D	0.529	neutral	D	0.687641953	None	None	N
N/I	0.9079	likely_pathogenic	0.8878	pathogenic	-0.006	Destabilizing	1.0	D	0.674	neutral	D	0.687393843	None	None	N
N/K	0.7801	likely_pathogenic	0.7335	pathogenic	0.015	Stabilizing	1.0	D	0.555	neutral	D	0.58840895	None	None	N
N/L	0.854	likely_pathogenic	0.8435	pathogenic	-0.006	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
N/M	0.8719	likely_pathogenic	0.8495	pathogenic	0.51	Stabilizing	1.0	D	0.578	neutral	None	None	None	None	N
N/P	0.988	likely_pathogenic	0.981	pathogenic	-0.116	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
N/Q	0.8305	likely_pathogenic	0.7954	pathogenic	-0.5	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
N/R	0.8259	likely_pathogenic	0.798	pathogenic	0.096	Stabilizing	1.0	D	0.564	neutral	None	None	None	None	N
N/S	0.3604	ambiguous	0.2966	benign	-0.199	Destabilizing	0.999	D	0.512	neutral	D	0.689402111	None	None	N
N/T	0.7398	likely_pathogenic	0.6647	pathogenic	-0.092	Destabilizing	0.999	D	0.554	neutral	D	0.688463286	None	None	N
N/V	0.9118	likely_pathogenic	0.8908	pathogenic	-0.116	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
N/W	0.9809	likely_pathogenic	0.9743	pathogenic	-0.675	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
N/Y	0.6074	likely_pathogenic	0.5816	pathogenic	-0.428	Destabilizing	1.0	D	0.593	neutral	D	0.687304674	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.