TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6910	20953;20954;20955	chr2:178725476;178725475;178725474	chr2:179590203;179590202;179590201
N2AB	6593	20002;20003;20004	chr2:178725476;178725475;178725474	chr2:179590203;179590202;179590201
N2A	5666	17221;17222;17223	chr2:178725476;178725475;178725474	chr2:179590203;179590202;179590201
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-53
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.0906
• 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/V	rs2079177597	None	0.37	N	0.488	0.205	0.195762928549	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
A/V	rs2079177597	None	0.37	N	0.488	0.205	0.195762928549	gnomAD-4.0.0	6.57333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78469E-04

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	0.6683	likely_pathogenic	0.6783	pathogenic	-0.785	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/D	0.9813	likely_pathogenic	0.9868	pathogenic	-1.736	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
A/E	0.955	likely_pathogenic	0.9661	pathogenic	-1.515	Destabilizing	0.999	D	0.763	deleterious	N	0.473493654	None	None	N
A/F	0.7551	likely_pathogenic	0.7653	pathogenic	-0.424	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
A/G	0.401	ambiguous	0.4031	ambiguous	-1.195	Destabilizing	0.996	D	0.642	neutral	N	0.504309065	None	None	N
A/H	0.9674	likely_pathogenic	0.9704	pathogenic	-1.769	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/I	0.4329	ambiguous	0.487	ambiguous	0.701	Stabilizing	0.967	D	0.705	prob.neutral	None	None	None	None	N
A/K	0.9824	likely_pathogenic	0.9861	pathogenic	-0.63	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
A/L	0.421	ambiguous	0.4616	ambiguous	0.701	Stabilizing	0.967	D	0.697	prob.neutral	None	None	None	None	N
A/M	0.5497	ambiguous	0.5804	pathogenic	0.33	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
A/N	0.9417	likely_pathogenic	0.9494	pathogenic	-0.977	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
A/P	0.9493	likely_pathogenic	0.9625	pathogenic	0.286	Stabilizing	0.999	D	0.793	deleterious	N	0.491597909	None	None	N
A/Q	0.9363	likely_pathogenic	0.9424	pathogenic	-0.717	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
A/R	0.9594	likely_pathogenic	0.9663	pathogenic	-0.944	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
A/S	0.3073	likely_benign	0.3107	benign	-1.434	Destabilizing	0.989	D	0.644	neutral	N	0.494051999	None	None	N
A/T	0.2423	likely_benign	0.2672	benign	-1.065	Destabilizing	0.978	D	0.644	neutral	N	0.471212248	None	None	N
A/V	0.1757	likely_benign	0.2057	benign	0.286	Stabilizing	0.37	N	0.488	neutral	N	0.473639441	None	None	N
A/W	0.9795	likely_pathogenic	0.9823	pathogenic	-1.23	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/Y	0.9248	likely_pathogenic	0.9264	pathogenic	-0.578	Destabilizing	0.999	D	0.803	deleterious	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.