TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21272	64039;64040;64041	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
N2AB	19631	59116;59117;59118	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
N2A	18704	56335;56336;56337	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
N2B	12207	36844;36845;36846	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
Novex-1	12332	37219;37220;37221	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
Novex-2	12399	37420;37421;37422	chr2:178587397;178587396;178587395	chr2:179452124;179452123;179452122
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-42
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6094
• 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
D/E	None	None	None	N	0.119	0.066	0.101711395817	gnomAD-4.0.0	6.85636E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00669E-07	0	0
D/Y	rs376015249	0.265	0.741	N	0.335	0.294	0.523754170085	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.2E-06	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
D/A	0.1312	likely_benign	0.159	benign	-0.307	Destabilizing	0.027	N	0.275	neutral	N	0.467591408	None	None	N
D/C	0.4235	ambiguous	0.4968	ambiguous	0.047	Stabilizing	0.935	D	0.326	neutral	None	None	None	None	N
D/E	0.1142	likely_benign	0.1433	benign	-0.316	Destabilizing	None	N	0.119	neutral	N	0.475768175	None	None	N
D/F	0.4638	ambiguous	0.563	ambiguous	-0.257	Destabilizing	0.555	D	0.342	neutral	None	None	None	None	N
D/G	0.1295	likely_benign	0.1422	benign	-0.496	Destabilizing	None	N	0.095	neutral	N	0.434593556	None	None	N
D/H	0.1906	likely_benign	0.2353	benign	-0.082	Destabilizing	0.317	N	0.376	neutral	N	0.478867195	None	None	N
D/I	0.2782	likely_benign	0.3748	ambiguous	0.143	Stabilizing	0.235	N	0.359	neutral	None	None	None	None	N
D/K	0.2893	likely_benign	0.3435	ambiguous	0.384	Stabilizing	0.081	N	0.3	neutral	None	None	None	None	N
D/L	0.2698	likely_benign	0.3319	benign	0.143	Stabilizing	0.081	N	0.375	neutral	None	None	None	None	N
D/M	0.4388	ambiguous	0.5362	ambiguous	0.279	Stabilizing	0.824	D	0.304	neutral	None	None	None	None	N
D/N	0.0784	likely_benign	0.0847	benign	0.04	Stabilizing	None	N	0.161	neutral	N	0.396667099	None	None	N
D/P	0.5457	ambiguous	0.6342	pathogenic	0.015	Stabilizing	0.555	D	0.403	neutral	None	None	None	None	N
D/Q	0.2112	likely_benign	0.2622	benign	0.067	Stabilizing	0.235	N	0.359	neutral	None	None	None	None	N
D/R	0.3173	likely_benign	0.3792	ambiguous	0.523	Stabilizing	0.38	N	0.349	neutral	None	None	None	None	N
D/S	0.0961	likely_benign	0.1107	benign	-0.049	Destabilizing	0.035	N	0.25	neutral	None	None	None	None	N
D/T	0.1777	likely_benign	0.23	benign	0.102	Stabilizing	0.081	N	0.309	neutral	None	None	None	None	N
D/V	0.1713	likely_benign	0.2283	benign	0.015	Stabilizing	0.002	N	0.27	neutral	N	0.492239137	None	None	N
D/W	0.8181	likely_pathogenic	0.8691	pathogenic	-0.12	Destabilizing	0.935	D	0.495	neutral	None	None	None	None	N
D/Y	0.2035	likely_benign	0.2397	benign	-0.016	Destabilizing	0.741	D	0.335	neutral	N	0.49274195	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.