TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19010	57253;57254;57255	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
N2AB	17369	52330;52331;52332	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
N2A	16442	49549;49550;49551	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
N2B	9945	30058;30059;30060	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
Novex-1	10070	30433;30434;30435	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
Novex-2	10137	30634;30635;30636	chr2:178598589;178598588;178598587	chr2:179463316;179463315;179463314
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: Fn3-26
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3621
• 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
S/A	rs758709446	-0.248	0.005	N	0.188	0.051	0.141422826196	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	5.74E-05	None	0	None	0	0	0
S/A	rs758709446	-0.248	0.005	N	0.188	0.051	0.141422826196	gnomAD-4.0.0	1.60333E-06	None	None	None	None	N	None	0	0	None	0	2.7908E-05	None	0	0	0	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	0.0815	likely_benign	0.0778	benign	-0.329	Destabilizing	0.005	N	0.188	neutral	N	0.461878945	None	None	N
S/C	0.1024	likely_benign	0.0923	benign	-0.232	Destabilizing	0.295	N	0.437	neutral	N	0.500898693	None	None	N
S/D	0.4164	ambiguous	0.4068	ambiguous	-0.399	Destabilizing	0.072	N	0.252	neutral	None	None	None	None	N
S/E	0.4232	ambiguous	0.4014	ambiguous	-0.289	Destabilizing	0.072	N	0.266	neutral	None	None	None	None	N
S/F	0.148	likely_benign	0.145	benign	-0.319	Destabilizing	0.055	N	0.533	neutral	N	0.514462636	None	None	N
S/G	0.0981	likely_benign	0.0953	benign	-0.665	Destabilizing	0.031	N	0.251	neutral	None	None	None	None	N
S/H	0.278	likely_benign	0.2655	benign	-1.091	Destabilizing	0.628	D	0.44	neutral	None	None	None	None	N
S/I	0.0783	likely_benign	0.0869	benign	0.482	Stabilizing	None	N	0.245	neutral	None	None	None	None	N
S/K	0.5159	ambiguous	0.492	ambiguous	-0.313	Destabilizing	0.072	N	0.26	neutral	None	None	None	None	N
S/L	0.0663	likely_benign	0.0672	benign	0.482	Stabilizing	0.003	N	0.325	neutral	None	None	None	None	N
S/M	0.1066	likely_benign	0.1119	benign	0.308	Stabilizing	0.003	N	0.262	neutral	None	None	None	None	N
S/N	0.1006	likely_benign	0.1054	benign	-0.652	Destabilizing	0.072	N	0.284	neutral	None	None	None	None	N
S/P	0.6166	likely_pathogenic	0.6083	pathogenic	0.248	Stabilizing	0.106	N	0.511	neutral	N	0.510248894	None	None	N
S/Q	0.3434	ambiguous	0.3373	benign	-0.502	Destabilizing	0.136	N	0.399	neutral	None	None	None	None	N
S/R	0.4994	ambiguous	0.4686	ambiguous	-0.518	Destabilizing	0.072	N	0.502	neutral	None	None	None	None	N
S/T	0.0615	likely_benign	0.0653	benign	-0.45	Destabilizing	None	N	0.064	neutral	N	0.436903142	None	None	N
S/V	0.1051	likely_benign	0.1108	benign	0.248	Stabilizing	None	N	0.261	neutral	None	None	None	None	N
S/W	0.3468	ambiguous	0.3343	benign	-0.566	Destabilizing	0.864	D	0.488	neutral	None	None	None	None	N
S/Y	0.1601	likely_benign	0.1465	benign	-0.129	Destabilizing	0.295	N	0.59	neutral	N	0.500725334	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.