TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32616	98071;98072;98073	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
N2AB	30975	93148;93149;93150	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
N2A	30048	90367;90368;90369	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
N2B	23551	70876;70877;70878	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
Novex-1	23676	71251;71252;71253	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
Novex-2	23743	71452;71453;71454	chr2:178540320;178540319;178540318	chr2:179405047;179405046;179405045
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-126
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1605
• 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
S/T	None	None	0.999	N	0.489	0.322	0.402614778071	gnomAD-4.0.0	3.60098E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93752E-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
S/A	0.2561	likely_benign	0.2275	benign	-0.384	Destabilizing	0.997	D	0.461	neutral	N	0.493914628	None	None	N
S/C	0.3736	ambiguous	0.3866	ambiguous	-0.812	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
S/D	0.9555	likely_pathogenic	0.9519	pathogenic	-1.651	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
S/E	0.9656	likely_pathogenic	0.9557	pathogenic	-1.639	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
S/F	0.8663	likely_pathogenic	0.8552	pathogenic	-1.028	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/G	0.4217	ambiguous	0.3907	ambiguous	-0.554	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	N
S/H	0.8704	likely_pathogenic	0.8686	pathogenic	-1.159	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
S/I	0.9019	likely_pathogenic	0.8965	pathogenic	-0.04	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
S/K	0.988	likely_pathogenic	0.9858	pathogenic	-0.47	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
S/L	0.6538	likely_pathogenic	0.6462	pathogenic	-0.04	Destabilizing	1.0	D	0.748	deleterious	D	0.530580891	None	None	N
S/M	0.6218	likely_pathogenic	0.6268	pathogenic	0.227	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
S/N	0.727	likely_pathogenic	0.7359	pathogenic	-0.838	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	N
S/P	0.9983	likely_pathogenic	0.9984	pathogenic	-0.126	Destabilizing	1.0	D	0.813	deleterious	D	0.530580891	None	None	N
S/Q	0.9371	likely_pathogenic	0.9225	pathogenic	-1.143	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
S/R	0.9795	likely_pathogenic	0.9763	pathogenic	-0.289	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/T	0.1278	likely_benign	0.1515	benign	-0.609	Destabilizing	0.999	D	0.489	neutral	N	0.478928697	None	None	N
S/V	0.791	likely_pathogenic	0.7871	pathogenic	-0.126	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
S/W	0.9178	likely_pathogenic	0.9149	pathogenic	-1.148	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/Y	0.8227	likely_pathogenic	0.81	pathogenic	-0.71	Destabilizing	1.0	D	0.839	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.