TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30856	92791;92792;92793	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
N2AB	29215	87868;87869;87870	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
N2A	28288	85087;85088;85089	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
N2B	21791	65596;65597;65598	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
Novex-1	21916	65971;65972;65973	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
Novex-2	21983	66172;66173;66174	chr2:178549060;178549059;178549058	chr2:179413787;179413786;179413785
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-113
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1088
• 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
Y/C	rs1698314860	None	1.0	D	0.88	0.878	0.856475289213	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1698314860	None	1.0	D	0.88	0.878	0.856475289213	gnomAD-4.0.0	2.56197E-06	None	None	None	None	N	None	1.69165E-05	0	None	0	0	None	0	0	2.39271E-06	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
Y/A	0.9961	likely_pathogenic	0.9958	pathogenic	-3.471	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/C	0.8845	likely_pathogenic	0.871	pathogenic	-1.906	Destabilizing	1.0	D	0.88	deleterious	D	0.646249523	None	None	N
Y/D	0.9939	likely_pathogenic	0.9926	pathogenic	-3.811	Highly Destabilizing	1.0	D	0.915	deleterious	D	0.662470688	None	None	N
Y/E	0.9987	likely_pathogenic	0.9984	pathogenic	-3.596	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/F	0.3046	likely_benign	0.2915	benign	-1.335	Destabilizing	0.999	D	0.638	neutral	N	0.51652074	None	None	N
Y/G	0.9862	likely_pathogenic	0.9852	pathogenic	-3.878	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
Y/H	0.9704	likely_pathogenic	0.9649	pathogenic	-2.561	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.646047719	None	None	N
Y/I	0.982	likely_pathogenic	0.9817	pathogenic	-2.091	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9984	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/L	0.9623	likely_pathogenic	0.9634	pathogenic	-2.091	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
Y/M	0.984	likely_pathogenic	0.9837	pathogenic	-1.812	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/N	0.9528	likely_pathogenic	0.9474	pathogenic	-3.184	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.662470688	None	None	N
Y/P	0.9989	likely_pathogenic	0.999	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.938	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.9977	pathogenic	-2.925	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/R	0.9953	likely_pathogenic	0.9947	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/S	0.9808	likely_pathogenic	0.9784	pathogenic	-3.492	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.662470688	None	None	N
Y/T	0.9945	likely_pathogenic	0.994	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.9643	likely_pathogenic	0.9641	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/W	0.862	likely_pathogenic	0.8632	pathogenic	-0.575	Destabilizing	1.0	D	0.8	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.