TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35625	107098;107099;107100	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
N2AB	33984	102175;102176;102177	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
N2A	33057	99394;99395;99396	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
N2B	26560	79903;79904;79905	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
Novex-1	26685	80278;80279;80280	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
Novex-2	26752	80479;80480;80481	chr2:178528878;178528877;178528876	chr2:179393605;179393604;179393603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-167
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2504
• 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
V/L	rs1687747331	None	0.001	N	0.419	0.108	0.19670166235	gnomAD-4.0.0	1.59091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85758E-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
V/A	0.1512	likely_benign	0.1543	benign	-0.945	Destabilizing	None	N	0.247	neutral	N	0.410553542	None	None	N
V/C	0.716	likely_pathogenic	0.741	pathogenic	-0.784	Destabilizing	0.356	N	0.473	neutral	None	None	None	None	N
V/D	0.2528	likely_benign	0.2754	benign	-0.653	Destabilizing	0.055	N	0.483	neutral	N	0.410900259	None	None	N
V/E	0.2238	likely_benign	0.2308	benign	-0.701	Destabilizing	0.031	N	0.447	neutral	None	None	None	None	N
V/F	0.1508	likely_benign	0.1504	benign	-0.789	Destabilizing	0.055	N	0.503	neutral	N	0.4107269	None	None	N
V/G	0.2286	likely_benign	0.2416	benign	-1.187	Destabilizing	0.012	N	0.419	neutral	N	0.411073617	None	None	N
V/H	0.4269	ambiguous	0.4289	ambiguous	-0.633	Destabilizing	0.628	D	0.51	neutral	None	None	None	None	N
V/I	0.0788	likely_benign	0.0772	benign	-0.415	Destabilizing	0.012	N	0.374	neutral	N	0.40968675	None	None	N
V/K	0.2904	likely_benign	0.2985	benign	-0.868	Destabilizing	0.031	N	0.444	neutral	None	None	None	None	N
V/L	0.1582	likely_benign	0.1531	benign	-0.415	Destabilizing	0.001	N	0.419	neutral	N	0.409513392	None	None	N
V/M	0.1363	likely_benign	0.1341	benign	-0.436	Destabilizing	0.003	N	0.342	neutral	None	None	None	None	N
V/N	0.1765	likely_benign	0.1781	benign	-0.64	Destabilizing	0.072	N	0.483	neutral	None	None	None	None	N
V/P	0.5835	likely_pathogenic	0.6487	pathogenic	-0.555	Destabilizing	0.136	N	0.513	neutral	None	None	None	None	N
V/Q	0.2486	likely_benign	0.2461	benign	-0.826	Destabilizing	0.136	N	0.523	neutral	None	None	None	None	N
V/R	0.2575	likely_benign	0.2656	benign	-0.324	Destabilizing	0.072	N	0.51	neutral	None	None	None	None	N
V/S	0.1423	likely_benign	0.1434	benign	-1.096	Destabilizing	0.007	N	0.4	neutral	None	None	None	None	N
V/T	0.0915	likely_benign	0.0912	benign	-1.031	Destabilizing	None	N	0.229	neutral	None	None	None	None	N
V/W	0.7499	likely_pathogenic	0.7461	pathogenic	-0.912	Destabilizing	0.864	D	0.521	neutral	None	None	None	None	N
V/Y	0.4615	ambiguous	0.4529	ambiguous	-0.628	Destabilizing	0.356	N	0.541	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.