TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8009	24250;24251;24252	chr2:178719365;178719364;178719363	chr2:179584092;179584091;179584090
N2AB	7692	23299;23300;23301	chr2:178719365;178719364;178719363	chr2:179584092;179584091;179584090
N2A	6765	20518;20519;20520	chr2:178719365;178719364;178719363	chr2:179584092;179584091;179584090
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-65
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4389
• Predicted PPI site: I

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
S/F	rs759900757	-0.743	0.781	N	0.636	0.428	0.758948374077	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
S/F	rs759900757	-0.743	0.781	N	0.636	0.428	0.758948374077	gnomAD-4.0.0	1.11389E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.71507E-05	0	3.02407E-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
S/A	0.0664	likely_benign	0.062	benign	-0.448	Destabilizing	0.001	N	0.159	neutral	N	0.491327565	None	None	I
S/C	0.1468	likely_benign	0.151	benign	-0.331	Destabilizing	0.931	D	0.563	neutral	N	0.503902851	None	None	I
S/D	0.609	likely_pathogenic	0.6419	pathogenic	0.497	Stabilizing	0.7	D	0.493	neutral	None	None	None	None	I
S/E	0.6357	likely_pathogenic	0.647	pathogenic	0.445	Stabilizing	0.399	N	0.473	neutral	None	None	None	None	I
S/F	0.1792	likely_benign	0.1766	benign	-0.882	Destabilizing	0.781	D	0.636	neutral	N	0.488912468	None	None	I
S/G	0.1416	likely_benign	0.1452	benign	-0.619	Destabilizing	0.121	N	0.437	neutral	None	None	None	None	I
S/H	0.4542	ambiguous	0.4697	ambiguous	-1.069	Destabilizing	0.982	D	0.564	neutral	None	None	None	None	I
S/I	0.2362	likely_benign	0.2241	benign	-0.12	Destabilizing	0.7	D	0.631	neutral	None	None	None	None	I
S/K	0.7974	likely_pathogenic	0.7955	pathogenic	-0.347	Destabilizing	0.399	N	0.471	neutral	None	None	None	None	I
S/L	0.1028	likely_benign	0.0994	benign	-0.12	Destabilizing	0.25	N	0.511	neutral	None	None	None	None	I
S/M	0.2223	likely_benign	0.216	benign	0.018	Stabilizing	0.947	D	0.565	neutral	None	None	None	None	I
S/N	0.2886	likely_benign	0.3072	benign	-0.183	Destabilizing	0.826	D	0.508	neutral	None	None	None	None	I
S/P	0.8341	likely_pathogenic	0.8378	pathogenic	-0.198	Destabilizing	0.638	D	0.595	neutral	N	0.501256278	None	None	I
S/Q	0.6016	likely_pathogenic	0.6011	pathogenic	-0.345	Destabilizing	0.826	D	0.554	neutral	None	None	None	None	I
S/R	0.7107	likely_pathogenic	0.7008	pathogenic	-0.247	Destabilizing	0.7	D	0.602	neutral	None	None	None	None	I
S/T	0.1046	likely_benign	0.0995	benign	-0.298	Destabilizing	0.201	N	0.406	neutral	N	0.457060276	None	None	I
S/V	0.2059	likely_benign	0.1933	benign	-0.198	Destabilizing	0.25	N	0.509	neutral	None	None	None	None	I
S/W	0.3347	likely_benign	0.3391	benign	-0.866	Destabilizing	0.982	D	0.654	neutral	None	None	None	None	I
S/Y	0.185	likely_benign	0.181	benign	-0.574	Destabilizing	0.781	D	0.625	neutral	D	0.523960058	None	None	I

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.