TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34346	103261;103262;103263	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
N2AB	32705	98338;98339;98340	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
N2A	31778	95557;95558;95559	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
N2B	25281	76066;76067;76068	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
Novex-1	25406	76441;76442;76443	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
Novex-2	25473	76642;76643;76644	chr2:178533579;178533578;178533577	chr2:179398306;179398305;179398304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-161
• Domain position: 89
• Structural Position: 172
• Q(SASA): 0.101
• 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/T	None	None	0.955	D	0.651	0.531	0.470730462751	gnomAD-4.0.0	1.59102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-06	0	0
A/V	None	None	0.977	D	0.674	0.404	0.513055635523	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88352E-05	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	0.9422	likely_pathogenic	0.9145	pathogenic	-1.023	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/D	0.9924	likely_pathogenic	0.9899	pathogenic	-1.944	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
A/E	0.9897	likely_pathogenic	0.9867	pathogenic	-1.803	Destabilizing	0.993	D	0.803	deleterious	D	0.554776257	None	None	N
A/F	0.9899	likely_pathogenic	0.9856	pathogenic	-0.755	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
A/G	0.2956	likely_benign	0.2836	benign	-1.431	Destabilizing	0.955	D	0.585	neutral	D	0.524752279	None	None	N
A/H	0.9969	likely_pathogenic	0.9956	pathogenic	-1.871	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/I	0.9873	likely_pathogenic	0.9773	pathogenic	0.153	Stabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
A/K	0.9979	likely_pathogenic	0.9975	pathogenic	-1.194	Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
A/L	0.9469	likely_pathogenic	0.9249	pathogenic	0.153	Stabilizing	0.983	D	0.776	deleterious	None	None	None	None	N
A/M	0.968	likely_pathogenic	0.9495	pathogenic	0.02	Stabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
A/N	0.9869	likely_pathogenic	0.9834	pathogenic	-1.304	Destabilizing	0.995	D	0.864	deleterious	None	None	None	None	N
A/P	0.9973	likely_pathogenic	0.9971	pathogenic	-0.182	Destabilizing	0.997	D	0.868	deleterious	D	0.555029747	None	None	N
A/Q	0.986	likely_pathogenic	0.9836	pathogenic	-1.199	Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
A/R	0.9905	likely_pathogenic	0.9896	pathogenic	-1.189	Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
A/S	0.416	ambiguous	0.3715	ambiguous	-1.733	Destabilizing	0.568	D	0.384	neutral	N	0.504298153	None	None	N
A/T	0.8268	likely_pathogenic	0.7414	pathogenic	-1.468	Destabilizing	0.955	D	0.651	neutral	D	0.536910713	None	None	N
A/V	0.9173	likely_pathogenic	0.8626	pathogenic	-0.182	Destabilizing	0.977	D	0.674	neutral	D	0.52676829	None	None	N
A/W	0.9991	likely_pathogenic	0.9986	pathogenic	-1.463	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/Y	0.9943	likely_pathogenic	0.9925	pathogenic	-0.902	Destabilizing	1.0	D	0.872	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.