TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14163	42712;42713;42714	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
N2AB	12522	37789;37790;37791	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
N2A	11595	35008;35009;35010	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
N2B	5098	15517;15518;15519	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
Novex-1	5223	15892;15893;15894	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
Novex-2	5290	16093;16094;16095	chr2:178634012;178634011;178634010	chr2:179498739;179498738;179498737
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-92
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0889
• 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/G	rs1310975229	-2.674	0.784	D	0.733	0.414	0.831548404372	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
C/G	rs1310975229	-2.674	0.784	D	0.733	0.414	0.831548404372	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	2.77531E-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	0.7797	likely_pathogenic	0.7967	pathogenic	-1.612	Destabilizing	0.465	N	0.498	neutral	None	None	None	None	N
C/D	0.9965	likely_pathogenic	0.9977	pathogenic	-1.721	Destabilizing	0.936	D	0.787	deleterious	None	None	None	None	N
C/E	0.9975	likely_pathogenic	0.9984	pathogenic	-1.472	Destabilizing	0.936	D	0.787	deleterious	None	None	None	None	N
C/F	0.3381	likely_benign	0.4661	ambiguous	-0.962	Destabilizing	0.001	N	0.518	neutral	N	0.48912493	None	None	N
C/G	0.6869	likely_pathogenic	0.6827	pathogenic	-1.976	Destabilizing	0.784	D	0.733	prob.delet.	D	0.63357904	None	None	N
C/H	0.9826	likely_pathogenic	0.9891	pathogenic	-2.237	Highly Destabilizing	0.981	D	0.801	deleterious	None	None	None	None	N
C/I	0.6604	likely_pathogenic	0.6933	pathogenic	-0.619	Destabilizing	0.329	N	0.623	neutral	None	None	None	None	N
C/K	0.9979	likely_pathogenic	0.9988	pathogenic	-1.271	Destabilizing	0.936	D	0.767	deleterious	None	None	None	None	N
C/L	0.6068	likely_pathogenic	0.6318	pathogenic	-0.619	Destabilizing	0.001	N	0.499	neutral	None	None	None	None	N
C/M	0.7683	likely_pathogenic	0.8264	pathogenic	0.195	Stabilizing	0.893	D	0.754	deleterious	None	None	None	None	N
C/N	0.9841	likely_pathogenic	0.9882	pathogenic	-1.944	Destabilizing	0.981	D	0.795	deleterious	None	None	None	None	N
C/P	0.9981	likely_pathogenic	0.9986	pathogenic	-0.928	Destabilizing	0.981	D	0.796	deleterious	None	None	None	None	N
C/Q	0.9909	likely_pathogenic	0.9944	pathogenic	-1.415	Destabilizing	0.981	D	0.8	deleterious	None	None	None	None	N
C/R	0.983	likely_pathogenic	0.9879	pathogenic	-1.729	Destabilizing	0.975	D	0.797	deleterious	D	0.634676543	None	None	N
C/S	0.8573	likely_pathogenic	0.8593	pathogenic	-2.21	Highly Destabilizing	0.6	D	0.66	neutral	D	0.593861326	None	None	N
C/T	0.8305	likely_pathogenic	0.8378	pathogenic	-1.78	Destabilizing	0.665	D	0.657	neutral	None	None	None	None	N
C/V	0.5409	ambiguous	0.5709	pathogenic	-0.928	Destabilizing	0.329	N	0.624	neutral	None	None	None	None	N
C/W	0.9053	likely_pathogenic	0.937	pathogenic	-1.442	Destabilizing	0.975	D	0.787	deleterious	D	0.634676543	None	None	N
C/Y	0.8287	likely_pathogenic	0.8717	pathogenic	-1.225	Destabilizing	0.473	N	0.715	prob.delet.	D	0.63357904	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.