TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7031	21316;21317;21318	chr2:178724284;178724283;178724282	chr2:179589011;179589010;179589009
N2AB	6714	20365;20366;20367	chr2:178724284;178724283;178724282	chr2:179589011;179589010;179589009
N2A	5787	17584;17585;17586	chr2:178724284;178724283;178724282	chr2:179589011;179589010;179589009
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-54
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1051
• 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
C/Y	rs1312705676	-1.393	1.0	N	0.879	0.426	0.789026292194	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
C/Y	rs1312705676	-1.393	1.0	N	0.879	0.426	0.789026292194	gnomAD-4.0.0	1.59275E-06	None	None	None	None	N	None	0	0	None	0	2.77654E-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
C/A	0.5263	ambiguous	0.6131	pathogenic	-1.703	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
C/D	0.8068	likely_pathogenic	0.8927	pathogenic	0.063	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
C/E	0.9187	likely_pathogenic	0.9577	pathogenic	0.143	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
C/F	0.447	ambiguous	0.5102	ambiguous	-1.167	Destabilizing	1.0	D	0.881	deleterious	N	0.480841212	None	None	N
C/G	0.3077	likely_benign	0.3993	ambiguous	-1.988	Destabilizing	1.0	D	0.82	deleterious	N	0.458753787	None	None	N
C/H	0.8557	likely_pathogenic	0.8935	pathogenic	-1.942	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
C/I	0.7375	likely_pathogenic	0.8057	pathogenic	-0.981	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
C/K	0.9649	likely_pathogenic	0.9806	pathogenic	-0.642	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
C/L	0.7278	likely_pathogenic	0.7758	pathogenic	-0.981	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
C/M	0.7976	likely_pathogenic	0.8634	pathogenic	-0.179	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
C/N	0.7662	likely_pathogenic	0.8398	pathogenic	-0.54	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
C/P	0.9971	likely_pathogenic	0.9965	pathogenic	-1.196	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
C/Q	0.8702	likely_pathogenic	0.9173	pathogenic	-0.488	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
C/R	0.8201	likely_pathogenic	0.8634	pathogenic	-0.519	Destabilizing	1.0	D	0.883	deleterious	N	0.449075511	None	None	N
C/S	0.3333	likely_benign	0.4048	ambiguous	-1.133	Destabilizing	1.0	D	0.774	deleterious	N	0.396337104	None	None	N
C/T	0.543	ambiguous	0.6315	pathogenic	-0.866	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
C/V	0.6337	likely_pathogenic	0.6922	pathogenic	-1.196	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
C/W	0.8685	likely_pathogenic	0.8879	pathogenic	-1.078	Destabilizing	1.0	D	0.843	deleterious	N	0.497792177	None	None	N
C/Y	0.7167	likely_pathogenic	0.7729	pathogenic	-1.072	Destabilizing	1.0	D	0.879	deleterious	N	0.493135719	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.