TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26735	80428;80429;80430	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
N2AB	25094	75505;75506;75507	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
N2A	24167	72724;72725;72726	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
N2B	17670	53233;53234;53235	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
Novex-1	17795	53608;53609;53610	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
Novex-2	17862	53809;53810;53811	chr2:178565929;178565928;178565927	chr2:179430656;179430655;179430654
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-82
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6109
• 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/G	None	None	0.012	N	0.208	0.106	0.104622674875	gnomAD-4.0.0	6.84271E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	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	0.0663	likely_benign	0.0661	benign	-0.512	Destabilizing	None	N	0.091	neutral	None	None	None	None	N
S/C	0.0989	likely_benign	0.1073	benign	-0.309	Destabilizing	0.295	N	0.326	neutral	N	0.474841959	None	None	N
S/D	0.3183	likely_benign	0.3944	ambiguous	-0.297	Destabilizing	0.016	N	0.179	neutral	None	None	None	None	N
S/E	0.413	ambiguous	0.4903	ambiguous	-0.372	Destabilizing	0.016	N	0.179	neutral	None	None	None	None	N
S/F	0.208	likely_benign	0.2442	benign	-1.015	Destabilizing	0.356	N	0.321	neutral	None	None	None	None	N
S/G	0.0698	likely_benign	0.0737	benign	-0.663	Destabilizing	0.012	N	0.208	neutral	N	0.485390522	None	None	N
S/H	0.2733	likely_benign	0.3043	benign	-1.246	Destabilizing	0.214	N	0.335	neutral	None	None	None	None	N
S/I	0.1268	likely_benign	0.1504	benign	-0.236	Destabilizing	0.055	N	0.319	neutral	N	0.491180344	None	None	N
S/K	0.5423	ambiguous	0.6152	pathogenic	-0.626	Destabilizing	0.016	N	0.183	neutral	None	None	None	None	N
S/L	0.0905	likely_benign	0.1014	benign	-0.236	Destabilizing	0.016	N	0.259	neutral	None	None	None	None	N
S/M	0.1554	likely_benign	0.1737	benign	0.22	Stabilizing	0.356	N	0.335	neutral	None	None	None	None	N
S/N	0.087	likely_benign	0.0995	benign	-0.409	Destabilizing	None	N	0.087	neutral	N	0.437191144	None	None	N
S/P	0.1283	likely_benign	0.1295	benign	-0.298	Destabilizing	0.136	N	0.327	neutral	None	None	None	None	N
S/Q	0.3465	ambiguous	0.3929	ambiguous	-0.723	Destabilizing	0.072	N	0.255	neutral	None	None	None	None	N
S/R	0.519	ambiguous	0.5755	pathogenic	-0.381	Destabilizing	0.055	N	0.284	neutral	N	0.476730967	None	None	N
S/T	0.0711	likely_benign	0.0759	benign	-0.479	Destabilizing	None	N	0.087	neutral	N	0.381721863	None	None	N
S/V	0.1146	likely_benign	0.1325	benign	-0.298	Destabilizing	0.016	N	0.26	neutral	None	None	None	None	N
S/W	0.3762	ambiguous	0.4049	ambiguous	-0.983	Destabilizing	0.864	D	0.346	neutral	None	None	None	None	N
S/Y	0.1985	likely_benign	0.2246	benign	-0.719	Destabilizing	0.628	D	0.32	neutral	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.