TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23483	70672;70673;70674	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
N2AB	21842	65749;65750;65751	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
N2A	20915	62968;62969;62970	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
N2B	14418	43477;43478;43479	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
Novex-1	14543	43852;43853;43854	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
Novex-2	14610	44053;44054;44055	chr2:178575685;178575684;178575683	chr2:179440412;179440411;179440410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-58
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4474
• 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/Y	None	None	0.932	N	0.383	0.408	0.581503058331	gnomAD-4.0.0	1.59171E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85904E-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	0.0721	likely_benign	0.0697	benign	-0.647	Destabilizing	None	N	0.115	neutral	N	0.449869652	None	None	N
S/C	0.1088	likely_benign	0.114	benign	-0.451	Destabilizing	0.932	D	0.347	neutral	N	0.495259938	None	None	N
S/D	0.8024	likely_pathogenic	0.8056	pathogenic	0.329	Stabilizing	0.405	N	0.25	neutral	None	None	None	None	N
S/E	0.8232	likely_pathogenic	0.8273	pathogenic	0.262	Stabilizing	0.488	N	0.26	neutral	None	None	None	None	N
S/F	0.2622	likely_benign	0.2671	benign	-1.078	Destabilizing	0.932	D	0.39	neutral	N	0.499298395	None	None	N
S/G	0.1301	likely_benign	0.1306	benign	-0.8	Destabilizing	0.207	N	0.311	neutral	None	None	None	None	N
S/H	0.535	ambiguous	0.5386	ambiguous	-1.193	Destabilizing	0.995	D	0.351	neutral	None	None	None	None	N
S/I	0.1629	likely_benign	0.1694	benign	-0.363	Destabilizing	0.817	D	0.375	neutral	None	None	None	None	N
S/K	0.9015	likely_pathogenic	0.906	pathogenic	-0.533	Destabilizing	0.718	D	0.263	neutral	None	None	None	None	N
S/L	0.1085	likely_benign	0.1075	benign	-0.363	Destabilizing	0.56	D	0.3	neutral	None	None	None	None	N
S/M	0.1738	likely_benign	0.1673	benign	-0.138	Destabilizing	0.948	D	0.353	neutral	None	None	None	None	N
S/N	0.2438	likely_benign	0.2414	benign	-0.319	Destabilizing	0.074	N	0.354	neutral	None	None	None	None	N
S/P	0.9299	likely_pathogenic	0.9137	pathogenic	-0.427	Destabilizing	0.002	N	0.203	neutral	N	0.48749803	None	None	N
S/Q	0.6327	likely_pathogenic	0.6445	pathogenic	-0.541	Destabilizing	0.948	D	0.393	neutral	None	None	None	None	N
S/R	0.8701	likely_pathogenic	0.8717	pathogenic	-0.326	Destabilizing	0.899	D	0.388	neutral	None	None	None	None	N
S/T	0.0694	likely_benign	0.0642	benign	-0.471	Destabilizing	None	N	0.117	neutral	N	0.423107126	None	None	N
S/V	0.1374	likely_benign	0.1393	benign	-0.427	Destabilizing	0.323	N	0.295	neutral	None	None	None	None	N
S/W	0.5983	likely_pathogenic	0.6205	pathogenic	-1.014	Destabilizing	0.995	D	0.468	neutral	None	None	None	None	N
S/Y	0.342	ambiguous	0.3551	ambiguous	-0.767	Destabilizing	0.932	D	0.383	neutral	N	0.519308308	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.