TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2132	6619;6620;6621	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
N2AB	2132	6619;6620;6621	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
N2A	2132	6619;6620;6621	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
N2B	2086	6481;6482;6483	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
Novex-1	2086	6481;6482;6483	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
Novex-2	2086	6481;6482;6483	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195
Novex-3	2132	6619;6620;6621	chr2:178775470;178775469;178775468	chr2:179640197;179640196;179640195

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-10
• Domain position: 55
• Structural Position: 134
• Q(SASA): 0.2877
• 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	0.121	N	0.347	0.193	0.224531998449	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
N/A	0.4777	ambiguous	0.5225	ambiguous	-0.805	Destabilizing	0.992	D	0.659	neutral	None	None	None	None	N
N/C	0.5156	ambiguous	0.5433	ambiguous	0.041	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
N/D	0.3252	likely_benign	0.3465	ambiguous	-0.46	Destabilizing	0.989	D	0.588	neutral	N	0.493547909	None	None	N
N/E	0.7492	likely_pathogenic	0.7782	pathogenic	-0.316	Destabilizing	0.983	D	0.604	neutral	None	None	None	None	N
N/F	0.7816	likely_pathogenic	0.806	pathogenic	-0.466	Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
N/G	0.4106	ambiguous	0.452	ambiguous	-1.175	Destabilizing	0.992	D	0.577	neutral	None	None	None	None	N
N/H	0.1763	likely_benign	0.187	benign	-0.793	Destabilizing	0.121	N	0.347	neutral	N	0.512060069	None	None	N
N/I	0.7105	likely_pathogenic	0.7341	pathogenic	0.154	Stabilizing	0.999	D	0.787	deleterious	D	0.593960116	None	None	N
N/K	0.6732	likely_pathogenic	0.6857	pathogenic	-0.146	Destabilizing	0.978	D	0.633	neutral	N	0.507511425	None	None	N
N/L	0.5401	ambiguous	0.56	ambiguous	0.154	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
N/M	0.6188	likely_pathogenic	0.6454	pathogenic	0.382	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
N/P	0.94	likely_pathogenic	0.9504	pathogenic	-0.137	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
N/Q	0.5674	likely_pathogenic	0.6057	pathogenic	-0.613	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
N/R	0.6215	likely_pathogenic	0.6376	pathogenic	-0.271	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
N/S	0.1142	likely_benign	0.1201	benign	-0.857	Destabilizing	0.989	D	0.571	neutral	N	0.498490791	None	None	N
N/T	0.3204	likely_benign	0.3414	ambiguous	-0.511	Destabilizing	0.989	D	0.659	neutral	N	0.50945732	None	None	N
N/V	0.6835	likely_pathogenic	0.7091	pathogenic	-0.137	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
N/W	0.9119	likely_pathogenic	0.9278	pathogenic	-0.273	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/Y	0.3517	ambiguous	0.3712	ambiguous	-0.016	Destabilizing	0.994	D	0.769	deleterious	D	0.593291149	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.