TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30942	93049;93050;93051	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
N2AB	29301	88126;88127;88128	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
N2A	28374	85345;85346;85347	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
N2B	21877	65854;65855;65856	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
Novex-1	22002	66229;66230;66231	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
Novex-2	22069	66430;66431;66432	chr2:178548802;178548801;178548800	chr2:179413529;179413528;179413527
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: Ig-150
• Domain position: 16
• Structural Position: 26
• Q(SASA): 0.4646
• 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
S/R	rs1575477437	None	0.968	N	0.406	0.24	0.272639205421	gnomAD-4.0.0	6.84699E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99463E-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	0.0998	likely_benign	0.103	benign	-0.454	Destabilizing	0.702	D	0.388	neutral	None	None	None	None	I
S/C	0.1791	likely_benign	0.195	benign	-0.3	Destabilizing	0.999	D	0.477	neutral	N	0.495449477	None	None	I
S/D	0.5736	likely_pathogenic	0.6345	pathogenic	-0.257	Destabilizing	0.919	D	0.358	neutral	None	None	None	None	I
S/E	0.7506	likely_pathogenic	0.8016	pathogenic	-0.323	Destabilizing	0.919	D	0.353	neutral	None	None	None	None	I
S/F	0.4495	ambiguous	0.4544	ambiguous	-0.885	Destabilizing	0.988	D	0.532	neutral	None	None	None	None	I
S/G	0.132	likely_benign	0.1418	benign	-0.625	Destabilizing	0.896	D	0.382	neutral	N	0.494435519	None	None	I
S/H	0.5688	likely_pathogenic	0.6254	pathogenic	-1.157	Destabilizing	0.999	D	0.468	neutral	None	None	None	None	I
S/I	0.3414	ambiguous	0.3741	ambiguous	-0.126	Destabilizing	0.968	D	0.443	neutral	N	0.483421609	None	None	I
S/K	0.8637	likely_pathogenic	0.9	pathogenic	-0.648	Destabilizing	0.919	D	0.361	neutral	None	None	None	None	I
S/L	0.2036	likely_benign	0.2077	benign	-0.126	Destabilizing	0.851	D	0.423	neutral	None	None	None	None	I
S/M	0.3246	likely_benign	0.328	benign	0.232	Stabilizing	0.999	D	0.465	neutral	None	None	None	None	I
S/N	0.2092	likely_benign	0.2512	benign	-0.439	Destabilizing	0.896	D	0.396	neutral	N	0.456199093	None	None	I
S/P	0.2491	likely_benign	0.2513	benign	-0.204	Destabilizing	0.988	D	0.397	neutral	None	None	None	None	I
S/Q	0.6993	likely_pathogenic	0.7515	pathogenic	-0.705	Destabilizing	0.988	D	0.424	neutral	None	None	None	None	I
S/R	0.8247	likely_pathogenic	0.8723	pathogenic	-0.398	Destabilizing	0.968	D	0.406	neutral	N	0.51127511	None	None	I
S/T	0.0929	likely_benign	0.0905	benign	-0.487	Destabilizing	0.016	N	0.192	neutral	N	0.442759174	None	None	I
S/V	0.2782	likely_benign	0.2979	benign	-0.204	Destabilizing	0.851	D	0.416	neutral	None	None	None	None	I
S/W	0.6283	likely_pathogenic	0.6326	pathogenic	-0.874	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
S/Y	0.431	ambiguous	0.4413	ambiguous	-0.611	Destabilizing	0.996	D	0.541	neutral	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.