TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32600	98023;98024;98025	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
N2AB	30959	93100;93101;93102	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
N2A	30032	90319;90320;90321	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
N2B	23535	70828;70829;70830	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
Novex-1	23660	71203;71204;71205	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
Novex-2	23727	71404;71405;71406	chr2:178540368;178540367;178540366	chr2:179405095;179405094;179405093
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-126
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6162
• 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
P/A	None	None	0.999	N	0.811	0.352	0.318252033908	gnomAD-4.0.0	1.59954E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87282E-06	0	0
P/T	None	None	1.0	N	0.828	0.379	0.547212138244	gnomAD-4.0.0	1.59954E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87282E-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
P/A	0.108	likely_benign	0.1279	benign	-0.411	Destabilizing	0.999	D	0.811	deleterious	N	0.4719044	None	None	I
P/C	0.5871	likely_pathogenic	0.6768	pathogenic	-0.564	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
P/D	0.8745	likely_pathogenic	0.9219	pathogenic	-0.211	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
P/E	0.5802	likely_pathogenic	0.6731	pathogenic	-0.333	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
P/F	0.6874	likely_pathogenic	0.7803	pathogenic	-0.865	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
P/G	0.6596	likely_pathogenic	0.7373	pathogenic	-0.509	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
P/H	0.4346	ambiguous	0.5545	ambiguous	-0.199	Destabilizing	1.0	D	0.853	deleterious	D	0.522310507	None	None	I
P/I	0.3444	ambiguous	0.4182	ambiguous	-0.309	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
P/K	0.4166	ambiguous	0.517	ambiguous	-0.093	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
P/L	0.1711	likely_benign	0.2126	benign	-0.309	Destabilizing	1.0	D	0.843	deleterious	N	0.482681729	None	None	I
P/M	0.4412	ambiguous	0.5103	ambiguous	-0.175	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/N	0.739	likely_pathogenic	0.8184	pathogenic	0.099	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/Q	0.2991	likely_benign	0.3773	ambiguous	-0.204	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
P/R	0.2769	likely_benign	0.366	ambiguous	0.352	Stabilizing	1.0	D	0.868	deleterious	N	0.502938804	None	None	I
P/S	0.2894	likely_benign	0.3703	ambiguous	-0.262	Destabilizing	1.0	D	0.839	deleterious	N	0.498165864	None	None	I
P/T	0.2402	likely_benign	0.3166	benign	-0.291	Destabilizing	1.0	D	0.828	deleterious	N	0.502685315	None	None	I
P/V	0.2337	likely_benign	0.2798	benign	-0.31	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
P/W	0.8729	likely_pathogenic	0.9279	pathogenic	-0.916	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/Y	0.6763	likely_pathogenic	0.7741	pathogenic	-0.552	Destabilizing	1.0	D	0.869	deleterious	None	None	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.