TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9915	29968;29969;29970	chr2:178704729;178704728;178704727	chr2:179569456;179569455;179569454
N2AB	9598	29017;29018;29019	chr2:178704729;178704728;178704727	chr2:179569456;179569455;179569454
N2A	8671	26236;26237;26238	chr2:178704729;178704728;178704727	chr2:179569456;179569455;179569454
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-84
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3369
• 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/T	None	None	0.012	None	0.27	0.11	0.158396225186	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	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	0.1906	likely_benign	0.2053	benign	-0.508	Destabilizing	0.016	N	0.387	neutral	None	None	None	None	N
N/C	0.346	ambiguous	0.4141	ambiguous	0.358	Stabilizing	0.676	D	0.456	neutral	None	None	None	None	N
N/D	0.0724	likely_benign	0.0746	benign	-0.616	Destabilizing	None	N	0.127	neutral	None	None	None	None	N
N/E	0.2081	likely_benign	0.2419	benign	-0.611	Destabilizing	None	N	0.105	neutral	None	None	None	None	N
N/F	0.6307	likely_pathogenic	0.6655	pathogenic	-0.668	Destabilizing	0.356	N	0.49	neutral	None	None	None	None	N
N/G	0.2248	likely_benign	0.258	benign	-0.754	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	N
N/H	0.1158	likely_benign	0.1284	benign	-0.803	Destabilizing	0.295	N	0.361	neutral	None	None	None	None	N
N/I	0.3099	likely_benign	0.3508	ambiguous	0.074	Stabilizing	0.171	N	0.511	neutral	None	None	None	None	N
N/K	0.1929	likely_benign	0.2331	benign	-0.161	Destabilizing	None	N	0.098	neutral	None	None	None	None	N
N/L	0.3294	likely_benign	0.3594	ambiguous	0.074	Stabilizing	0.072	N	0.488	neutral	None	None	None	None	N
N/M	0.3873	ambiguous	0.4269	ambiguous	0.715	Stabilizing	0.628	D	0.446	neutral	None	None	None	None	N
N/P	0.8479	likely_pathogenic	0.8992	pathogenic	-0.091	Destabilizing	0.136	N	0.477	neutral	None	None	None	None	N
N/Q	0.2346	likely_benign	0.2619	benign	-0.764	Destabilizing	0.038	N	0.259	neutral	None	None	None	None	N
N/R	0.2218	likely_benign	0.2554	benign	-0.061	Destabilizing	0.038	N	0.262	neutral	None	None	None	None	N
N/S	0.0754	likely_benign	0.0796	benign	-0.47	Destabilizing	None	N	0.135	neutral	None	None	None	None	N
N/T	0.133	likely_benign	0.1303	benign	-0.313	Destabilizing	0.012	N	0.27	neutral	None	None	None	None	N
N/V	0.2759	likely_benign	0.3132	benign	-0.091	Destabilizing	0.072	N	0.514	neutral	None	None	None	None	N
N/W	0.803	likely_pathogenic	0.8329	pathogenic	-0.565	Destabilizing	0.864	D	0.51	neutral	None	None	None	None	N
N/Y	0.2279	likely_benign	0.2394	benign	-0.328	Destabilizing	0.295	N	0.477	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.