TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4838	14737;14738;14739	chr2:178735934;178735933;178735932	chr2:179600661;179600660;179600659
N2AB	4521	13786;13787;13788	chr2:178735934;178735933;178735932	chr2:179600661;179600660;179600659
N2A	3594	11005;11006;11007	chr2:178735934;178735933;178735932	chr2:179600661;179600660;179600659
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: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-31
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.8466
• 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/L	rs758347900	0.017	0.002	D	0.205	0.198	0.366277470483	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
S/L	rs758347900	0.017	0.002	D	0.205	0.198	0.366277470483	gnomAD-4.0.0	4.77339E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57412E-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
S/A	0.0976	likely_benign	0.0886	benign	-0.329	Destabilizing	0.047	N	0.211	neutral	N	0.442927287	None	None	I
S/C	0.134	likely_benign	0.1185	benign	-0.269	Destabilizing	0.983	D	0.264	neutral	None	None	None	None	I
S/D	0.4165	ambiguous	0.3418	ambiguous	0.405	Stabilizing	0.002	N	0.143	neutral	None	None	None	None	I
S/E	0.5451	ambiguous	0.4867	ambiguous	0.347	Stabilizing	0.004	N	0.105	neutral	None	None	None	None	I
S/F	0.1851	likely_benign	0.1595	benign	-0.805	Destabilizing	0.557	D	0.263	neutral	None	None	None	None	I
S/G	0.1001	likely_benign	0.0829	benign	-0.482	Destabilizing	0.001	N	0.114	neutral	None	None	None	None	I
S/H	0.3252	likely_benign	0.2913	benign	-0.888	Destabilizing	0.94	D	0.26	neutral	None	None	None	None	I
S/I	0.1994	likely_benign	0.1658	benign	-0.051	Destabilizing	0.264	N	0.307	neutral	None	None	None	None	I
S/K	0.6548	likely_pathogenic	0.5841	pathogenic	-0.397	Destabilizing	0.418	N	0.223	neutral	None	None	None	None	I
S/L	0.0976	likely_benign	0.0871	benign	-0.051	Destabilizing	0.002	N	0.205	neutral	D	0.549196767	None	None	I
S/M	0.2515	likely_benign	0.2258	benign	-0.081	Destabilizing	0.716	D	0.261	neutral	None	None	None	None	I
S/N	0.1993	likely_benign	0.1533	benign	-0.182	Destabilizing	0.418	N	0.244	neutral	None	None	None	None	I
S/P	0.4497	ambiguous	0.3637	ambiguous	-0.112	Destabilizing	0.523	D	0.309	neutral	N	0.517809986	None	None	I
S/Q	0.5141	ambiguous	0.4692	ambiguous	-0.311	Destabilizing	0.418	N	0.229	neutral	None	None	None	None	I
S/R	0.6008	likely_pathogenic	0.5171	ambiguous	-0.266	Destabilizing	0.418	N	0.311	neutral	None	None	None	None	I
S/T	0.102	likely_benign	0.0918	benign	-0.249	Destabilizing	0.007	N	0.16	neutral	N	0.461139953	None	None	I
S/V	0.2024	likely_benign	0.1701	benign	-0.112	Destabilizing	0.264	N	0.288	neutral	None	None	None	None	I
S/W	0.3592	ambiguous	0.3271	benign	-0.869	Destabilizing	0.983	D	0.266	neutral	None	None	None	None	I
S/Y	0.1831	likely_benign	0.1672	benign	-0.563	Destabilizing	0.836	D	0.26	neutral	None	None	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.