TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32992	99199;99200;99201	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
N2AB	31351	94276;94277;94278	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
N2A	30424	91495;91496;91497	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
N2B	23927	72004;72005;72006	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
Novex-1	24052	72379;72380;72381	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
Novex-2	24119	72580;72581;72582	chr2:178538961;178538960;178538959	chr2:179403688;179403687;179403686
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: Fn3-128
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0591
• 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/S	rs754280430	-1.99	0.999	N	0.827	0.467	0.655633844924	gnomAD-4.0.0	1.60819E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43972E-05	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	0.8086	likely_pathogenic	0.8414	pathogenic	-1.248	Destabilizing	0.995	D	0.57	neutral	None	None	None	None	N
C/D	0.9995	likely_pathogenic	0.9996	pathogenic	-1.772	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
C/E	0.9996	likely_pathogenic	0.9997	pathogenic	-1.585	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
C/F	0.9588	likely_pathogenic	0.9652	pathogenic	-1.02	Destabilizing	0.999	D	0.835	deleterious	N	0.473941862	None	None	N
C/G	0.8713	likely_pathogenic	0.8955	pathogenic	-1.524	Destabilizing	0.999	D	0.832	deleterious	N	0.476983736	None	None	N
C/H	0.9984	likely_pathogenic	0.9986	pathogenic	-2.038	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
C/I	0.9001	likely_pathogenic	0.9146	pathogenic	-0.54	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
C/K	0.9997	likely_pathogenic	0.9997	pathogenic	-1.009	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
C/L	0.8593	likely_pathogenic	0.8853	pathogenic	-0.54	Destabilizing	0.998	D	0.701	prob.delet.	None	None	None	None	N
C/M	0.9709	likely_pathogenic	0.9768	pathogenic	-0.41	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
C/N	0.9948	likely_pathogenic	0.9961	pathogenic	-1.46	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
C/P	0.9847	likely_pathogenic	0.9812	pathogenic	-0.753	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
C/Q	0.9983	likely_pathogenic	0.9985	pathogenic	-1.138	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
C/R	0.9959	likely_pathogenic	0.9964	pathogenic	-1.389	Destabilizing	0.999	D	0.817	deleterious	N	0.477237226	None	None	N
C/S	0.915	likely_pathogenic	0.9347	pathogenic	-1.626	Destabilizing	0.999	D	0.827	deleterious	N	0.476223268	None	None	N
C/T	0.9303	likely_pathogenic	0.9474	pathogenic	-1.289	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
C/V	0.7961	likely_pathogenic	0.82	pathogenic	-0.753	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
C/W	0.9968	likely_pathogenic	0.997	pathogenic	-1.532	Destabilizing	1.0	D	0.797	deleterious	N	0.477997694	None	None	N
C/Y	0.9933	likely_pathogenic	0.9943	pathogenic	-1.178	Destabilizing	0.999	D	0.829	deleterious	N	0.476730247	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.