TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33403	100432;100433;100434	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
N2AB	31762	95509;95510;95511	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
N2A	30835	92728;92729;92730	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
N2B	24338	73237;73238;73239	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
Novex-1	24463	73612;73613;73614	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
Novex-2	24530	73813;73814;73815	chr2:178536540;178536539;178536538	chr2:179401267;179401266;179401265
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-131
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.2971
• 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
A/T	None	None	0.925	N	0.426	0.135	0.323886383625	gnomAD-4.0.0	7.33229E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.35657E-07	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
A/C	0.6203	likely_pathogenic	0.6256	pathogenic	-0.837	Destabilizing	1.0	D	0.491	neutral	None	None	None	None	N
A/D	0.4397	ambiguous	0.6247	pathogenic	-0.452	Destabilizing	0.961	D	0.613	neutral	N	0.378932274	None	None	N
A/E	0.4075	ambiguous	0.5996	pathogenic	-0.59	Destabilizing	0.97	D	0.515	neutral	None	None	None	None	N
A/F	0.5332	ambiguous	0.6401	pathogenic	-0.885	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
A/G	0.1568	likely_benign	0.1643	benign	-0.452	Destabilizing	0.031	N	0.147	neutral	N	0.40700431	None	None	N
A/H	0.6602	likely_pathogenic	0.76	pathogenic	-0.501	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
A/I	0.4933	ambiguous	0.5527	ambiguous	-0.345	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
A/K	0.6796	likely_pathogenic	0.838	pathogenic	-0.751	Destabilizing	0.97	D	0.52	neutral	None	None	None	None	N
A/L	0.3107	likely_benign	0.3742	ambiguous	-0.345	Destabilizing	0.985	D	0.527	neutral	None	None	None	None	N
A/M	0.3762	ambiguous	0.4302	ambiguous	-0.401	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
A/N	0.3581	ambiguous	0.4597	ambiguous	-0.461	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	N
A/P	0.8378	likely_pathogenic	0.9315	pathogenic	-0.317	Destabilizing	0.994	D	0.601	neutral	N	0.461665514	None	None	N
A/Q	0.5056	ambiguous	0.6277	pathogenic	-0.713	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
A/R	0.5951	likely_pathogenic	0.7678	pathogenic	-0.305	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	N
A/S	0.1041	likely_benign	0.1211	benign	-0.691	Destabilizing	0.287	N	0.135	neutral	N	0.387455757	None	None	N
A/T	0.1293	likely_benign	0.151	benign	-0.743	Destabilizing	0.925	D	0.426	neutral	N	0.451968595	None	None	N
A/V	0.2412	likely_benign	0.2761	benign	-0.317	Destabilizing	0.98	D	0.457	neutral	N	0.458337207	None	None	N
A/W	0.8842	likely_pathogenic	0.9303	pathogenic	-1.049	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
A/Y	0.6664	likely_pathogenic	0.7732	pathogenic	-0.696	Destabilizing	0.999	D	0.692	prob.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.