TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16226	48901;48902;48903	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
N2AB	14585	43978;43979;43980	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
N2A	13658	41197;41198;41199	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
N2B	7161	21706;21707;21708	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
Novex-1	7286	22081;22082;22083	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
Novex-2	7353	22282;22283;22284	chr2:178614931;178614930;178614929	chr2:179479658;179479657;179479656
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-5
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1144
• 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
A/G	None	None	0.41	N	0.623	0.219	0.489658423131	gnomAD-4.0.0	6.93103E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07647E-07	0	0
A/T	None	None	0.41	N	0.646	0.107	0.350088858571	gnomAD-4.0.0	1.38581E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81494E-06	0	0
A/V	None	None	0.581	N	0.68	0.174	0.499858025796	gnomAD-4.0.0	6.93103E-07	None	None	None	None	N	None	0	0	None	0	2.57268E-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
A/C	0.3187	likely_benign	0.3221	benign	-0.643	Destabilizing	0.98	D	0.717	prob.delet.	None	None	None	None	N
A/D	0.7023	likely_pathogenic	0.6798	pathogenic	-2.262	Highly Destabilizing	0.709	D	0.784	deleterious	N	0.4818366	None	None	N
A/E	0.5434	ambiguous	0.515	ambiguous	-2.025	Highly Destabilizing	0.764	D	0.758	deleterious	None	None	None	None	N
A/F	0.4295	ambiguous	0.4119	ambiguous	-0.486	Destabilizing	0.929	D	0.833	deleterious	None	None	None	None	N
A/G	0.1655	likely_benign	0.1664	benign	-1.391	Destabilizing	0.41	N	0.623	neutral	N	0.465825545	None	None	N
A/H	0.6136	likely_pathogenic	0.5841	pathogenic	-2.027	Highly Destabilizing	0.98	D	0.824	deleterious	None	None	None	None	N
A/I	0.3552	ambiguous	0.3784	ambiguous	0.456	Stabilizing	0.866	D	0.777	deleterious	None	None	None	None	N
A/K	0.7708	likely_pathogenic	0.7425	pathogenic	-0.864	Destabilizing	0.764	D	0.759	deleterious	None	None	None	None	N
A/L	0.2449	likely_benign	0.2453	benign	0.456	Stabilizing	0.648	D	0.749	deleterious	None	None	None	None	N
A/M	0.2734	likely_benign	0.288	benign	0.213	Stabilizing	0.993	D	0.779	deleterious	None	None	None	None	N
A/N	0.3853	ambiguous	0.3962	ambiguous	-1.254	Destabilizing	0.764	D	0.794	deleterious	None	None	None	None	N
A/P	0.9589	likely_pathogenic	0.9597	pathogenic	0.046	Stabilizing	0.83	D	0.781	deleterious	N	0.466256289	None	None	N
A/Q	0.436	ambiguous	0.4179	ambiguous	-0.967	Destabilizing	0.866	D	0.792	deleterious	None	None	None	None	N
A/R	0.6794	likely_pathogenic	0.6204	pathogenic	-1.142	Destabilizing	0.866	D	0.787	deleterious	None	None	None	None	N
A/S	0.0848	likely_benign	0.0909	benign	-1.6	Destabilizing	0.01	N	0.371	neutral	N	0.434298719	None	None	N
A/T	0.1113	likely_benign	0.1152	benign	-1.242	Destabilizing	0.41	N	0.646	neutral	N	0.455855891	None	None	N
A/V	0.2021	likely_benign	0.2055	benign	0.046	Stabilizing	0.581	D	0.68	prob.neutral	N	0.453011049	None	None	N
A/W	0.8363	likely_pathogenic	0.8222	pathogenic	-1.406	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
A/Y	0.5585	ambiguous	0.5497	ambiguous	-0.788	Destabilizing	0.98	D	0.829	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.