TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22871	68836;68837;68838	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
N2AB	21230	63913;63914;63915	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
N2A	20303	61132;61133;61134	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
N2B	13806	41641;41642;41643	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
Novex-1	13931	42016;42017;42018	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
Novex-2	13998	42217;42218;42219	chr2:178577815;178577814;178577813	chr2:179442542;179442541;179442540
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: Fn3-54
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3183
• Predicted PPI site: I

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/L	rs761622490	0.42	0.684	N	0.711	0.347	0.444505407614	gnomAD-2.1.1	1.62E-05	None	None	None	None	I	None	0	0	None	0	2.24568E-04	None	0	None	0	0	0
H/L	rs761622490	0.42	0.684	N	0.711	0.347	0.444505407614	gnomAD-4.0.0	4.7847E-06	None	None	None	None	I	None	0	0	None	0	8.34678E-05	None	0	0	0	0	0
H/R	rs761622490	-0.258	0.884	N	0.635	0.336	0.242825505644	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
H/R	rs761622490	-0.258	0.884	N	0.635	0.336	0.242825505644	gnomAD-4.0.0	3.1898E-06	None	None	None	None	I	None	5.67151E-05	0	None	0	0	None	0	0	0	0	3.02847E-05

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	0.7203	likely_pathogenic	0.7588	pathogenic	0.057	Stabilizing	0.59	D	0.612	neutral	None	None	None	None	I
H/C	0.2978	likely_benign	0.3267	benign	0.508	Stabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	I
H/D	0.7795	likely_pathogenic	0.8161	pathogenic	0.128	Stabilizing	0.684	D	0.635	neutral	N	0.453216602	None	None	I
H/E	0.8058	likely_pathogenic	0.8444	pathogenic	0.127	Stabilizing	0.742	D	0.606	neutral	None	None	None	None	I
H/F	0.4092	ambiguous	0.4519	ambiguous	0.341	Stabilizing	0.835	D	0.621	neutral	None	None	None	None	I
H/G	0.749	likely_pathogenic	0.7877	pathogenic	-0.183	Destabilizing	0.59	D	0.67	neutral	None	None	None	None	I
H/I	0.7693	likely_pathogenic	0.7899	pathogenic	0.649	Stabilizing	0.953	D	0.712	prob.delet.	None	None	None	None	I
H/K	0.6946	likely_pathogenic	0.7466	pathogenic	0.091	Stabilizing	0.742	D	0.648	neutral	None	None	None	None	I
H/L	0.3802	ambiguous	0.4109	ambiguous	0.649	Stabilizing	0.684	D	0.711	prob.delet.	N	0.444925193	None	None	I
H/M	0.7646	likely_pathogenic	0.789	pathogenic	0.618	Stabilizing	0.996	D	0.696	prob.neutral	None	None	None	None	I
H/N	0.3538	ambiguous	0.3748	ambiguous	0.251	Stabilizing	0.684	D	0.651	neutral	N	0.430033098	None	None	I
H/P	0.8859	likely_pathogenic	0.8956	pathogenic	0.477	Stabilizing	0.939	D	0.69	prob.neutral	N	0.489985479	None	None	I
H/Q	0.5391	ambiguous	0.5757	pathogenic	0.257	Stabilizing	0.884	D	0.637	neutral	N	0.450331012	None	None	I
H/R	0.414	ambiguous	0.4841	ambiguous	-0.193	Destabilizing	0.884	D	0.635	neutral	N	0.449117504	None	None	I
H/S	0.5435	ambiguous	0.5702	pathogenic	0.188	Stabilizing	0.037	N	0.439	neutral	None	None	None	None	I
H/T	0.788	likely_pathogenic	0.8131	pathogenic	0.277	Stabilizing	0.59	D	0.694	prob.neutral	None	None	None	None	I
H/V	0.7075	likely_pathogenic	0.7404	pathogenic	0.477	Stabilizing	0.91	D	0.713	prob.delet.	None	None	None	None	I
H/W	0.575	likely_pathogenic	0.6202	pathogenic	0.309	Stabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	I
H/Y	0.1441	likely_benign	0.1655	benign	0.703	Stabilizing	0.028	N	0.382	neutral	N	0.497796885	None	None	I

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.