TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25724	77395;77396;77397	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
N2AB	24083	72472;72473;72474	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
N2A	23156	69691;69692;69693	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
N2B	16659	50200;50201;50202	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
Novex-1	16784	50575;50576;50577	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
Novex-2	16851	50776;50777;50778	chr2:178568962;178568961;178568960	chr2:179433689;179433688;179433687
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-75
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5244
• 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
H/N	None	None	0.997	N	0.461	0.356	0.262662153117	gnomAD-4.0.0	1.59204E-06	None	None	None	None	N	None	5.6638E-05	0	None	0	0	None	0	0	0	0	0
H/R	None	-0.049	0.999	N	0.563	0.377	0.28058544554	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/R	None	-0.049	0.999	N	0.563	0.377	0.28058544554	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43324E-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
H/A	0.6356	likely_pathogenic	0.6913	pathogenic	0.598	Stabilizing	0.999	D	0.46	neutral	None	None	None	None	N
H/C	0.3747	ambiguous	0.4104	ambiguous	0.893	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
H/D	0.4775	ambiguous	0.5468	ambiguous	0.094	Stabilizing	0.999	D	0.529	neutral	N	0.446594487	None	None	N
H/E	0.6703	likely_pathogenic	0.7416	pathogenic	0.092	Stabilizing	0.998	D	0.452	neutral	None	None	None	None	N
H/F	0.3337	likely_benign	0.3537	ambiguous	0.985	Stabilizing	1.0	D	0.599	neutral	None	None	None	None	N
H/G	0.6223	likely_pathogenic	0.6662	pathogenic	0.363	Stabilizing	0.999	D	0.483	neutral	None	None	None	None	N
H/I	0.6091	likely_pathogenic	0.6945	pathogenic	1.17	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
H/K	0.6096	likely_pathogenic	0.643	pathogenic	0.569	Stabilizing	1.0	D	0.523	neutral	None	None	None	None	N
H/L	0.3515	ambiguous	0.4252	ambiguous	1.17	Stabilizing	0.999	D	0.637	neutral	N	0.516339787	None	None	N
H/M	0.6769	likely_pathogenic	0.7324	pathogenic	0.914	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
H/N	0.1772	likely_benign	0.1989	benign	0.62	Stabilizing	0.997	D	0.461	neutral	N	0.440380591	None	None	N
H/P	0.8866	likely_pathogenic	0.9017	pathogenic	1.005	Stabilizing	0.999	D	0.631	neutral	N	0.50014097	None	None	N
H/Q	0.4654	ambiguous	0.5308	ambiguous	0.649	Stabilizing	0.999	D	0.606	neutral	N	0.500620973	None	None	N
H/R	0.3395	likely_benign	0.3709	ambiguous	0.066	Stabilizing	0.999	D	0.563	neutral	N	0.483016647	None	None	N
H/S	0.4221	ambiguous	0.4658	ambiguous	0.723	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	N
H/T	0.5217	ambiguous	0.5922	pathogenic	0.812	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	N
H/V	0.5524	ambiguous	0.6335	pathogenic	1.005	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
H/W	0.5049	ambiguous	0.5046	ambiguous	0.861	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
H/Y	0.1256	likely_benign	0.1273	benign	1.222	Stabilizing	0.999	D	0.454	neutral	N	0.442690177	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.