TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29622	89089;89090;89091	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
N2AB	27981	84166;84167;84168	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
N2A	27054	81385;81386;81387	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
N2B	20557	61894;61895;61896	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
Novex-1	20682	62269;62270;62271	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
Novex-2	20749	62470;62471;62472	chr2:178554483;178554482;178554481	chr2:179419210;179419209;179419208
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: Fn3-103
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.2174
• 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/Y	rs1274325104	-0.563	0.999	D	0.873	0.466	0.695963169682	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
S/Y	rs1274325104	-0.563	0.999	D	0.873	0.466	0.695963169682	gnomAD-4.0.0	3.18379E-06	None	None	None	None	N	None	0	4.57457E-05	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
S/A	0.3568	ambiguous	0.4092	ambiguous	-0.606	Destabilizing	0.994	D	0.664	prob.neutral	N	0.49573828	None	None	N
S/C	0.4749	ambiguous	0.5079	ambiguous	-0.226	Destabilizing	1.0	D	0.806	deleterious	N	0.514629457	None	None	N
S/D	0.9748	likely_pathogenic	0.9774	pathogenic	0.096	Stabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
S/E	0.9913	likely_pathogenic	0.9928	pathogenic	0.209	Stabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
S/F	0.9808	likely_pathogenic	0.9869	pathogenic	-0.585	Destabilizing	0.999	D	0.874	deleterious	D	0.540874013	None	None	N
S/G	0.3409	ambiguous	0.3819	ambiguous	-0.953	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
S/H	0.9831	likely_pathogenic	0.9843	pathogenic	-1.206	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/I	0.9433	likely_pathogenic	0.9599	pathogenic	0.239	Stabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
S/K	0.9979	likely_pathogenic	0.9983	pathogenic	0.054	Stabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
S/L	0.8224	likely_pathogenic	0.8635	pathogenic	0.239	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
S/M	0.8126	likely_pathogenic	0.8544	pathogenic	0.164	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/N	0.9052	likely_pathogenic	0.9116	pathogenic	-0.258	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
S/P	0.992	likely_pathogenic	0.9943	pathogenic	-0.007	Destabilizing	0.999	D	0.879	deleterious	N	0.511248869	None	None	N
S/Q	0.9888	likely_pathogenic	0.9906	pathogenic	-0.153	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
S/R	0.9973	likely_pathogenic	0.998	pathogenic	-0.179	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
S/T	0.1764	likely_benign	0.21	benign	-0.198	Destabilizing	0.997	D	0.739	deleterious	N	0.511619905	None	None	N
S/V	0.8746	likely_pathogenic	0.9074	pathogenic	-0.007	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
S/W	0.9853	likely_pathogenic	0.9893	pathogenic	-0.653	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/Y	0.9753	likely_pathogenic	0.981	pathogenic	-0.261	Destabilizing	0.999	D	0.873	deleterious	D	0.551976829	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.