TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16401	49426;49427;49428	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
N2AB	14760	44503;44504;44505	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
N2A	13833	41722;41723;41724	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
N2B	7336	22231;22232;22233	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
Novex-1	7461	22606;22607;22608	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
Novex-2	7528	22807;22808;22809	chr2:178614196;178614195;178614194	chr2:179478923;179478922;179478921
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-6
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2815
• 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
L/R	None	None	0.997	D	0.833	0.5	0.814810762646	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/V	rs794729447	None	0.117	N	0.416	0.128	0.447213685739	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs794729447	None	0.117	N	0.416	0.128	0.447213685739	gnomAD-4.0.0	6.59031E-06	None	None	None	None	N	None	2.41838E-05	0	None	0	0	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
L/A	0.8238	likely_pathogenic	0.8261	pathogenic	-1.416	Destabilizing	0.966	D	0.589	neutral	None	None	None	None	N
L/C	0.8485	likely_pathogenic	0.8402	pathogenic	-1.003	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/D	0.9915	likely_pathogenic	0.9908	pathogenic	-0.348	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
L/E	0.9468	likely_pathogenic	0.9405	pathogenic	-0.266	Destabilizing	0.998	D	0.822	deleterious	None	None	None	None	N
L/F	0.552	ambiguous	0.561	ambiguous	-0.725	Destabilizing	0.993	D	0.771	deleterious	N	0.496698461	None	None	N
L/G	0.9767	likely_pathogenic	0.9755	pathogenic	-1.789	Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	N
L/H	0.9184	likely_pathogenic	0.9163	pathogenic	-0.825	Destabilizing	1.0	D	0.821	deleterious	N	0.469321437	None	None	N
L/I	0.1106	likely_benign	0.1098	benign	-0.442	Destabilizing	0.955	D	0.487	neutral	N	0.479973241	None	None	N
L/K	0.9506	likely_pathogenic	0.9478	pathogenic	-0.841	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
L/M	0.2284	likely_benign	0.2413	benign	-0.543	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
L/N	0.9558	likely_pathogenic	0.9544	pathogenic	-0.889	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
L/P	0.9767	likely_pathogenic	0.9774	pathogenic	-0.736	Destabilizing	0.999	D	0.834	deleterious	D	0.6259028	None	None	N
L/Q	0.852	likely_pathogenic	0.8492	pathogenic	-0.875	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
L/R	0.9374	likely_pathogenic	0.9337	pathogenic	-0.474	Destabilizing	0.997	D	0.833	deleterious	D	0.596685203	None	None	N
L/S	0.9484	likely_pathogenic	0.9497	pathogenic	-1.62	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
L/T	0.8206	likely_pathogenic	0.8217	pathogenic	-1.396	Destabilizing	0.995	D	0.762	deleterious	None	None	None	None	N
L/V	0.1454	likely_benign	0.1498	benign	-0.736	Destabilizing	0.117	N	0.416	neutral	N	0.391308452	None	None	N
L/W	0.8747	likely_pathogenic	0.8687	pathogenic	-0.815	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/Y	0.8633	likely_pathogenic	0.852	pathogenic	-0.559	Destabilizing	0.998	D	0.846	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.