TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35693	107302;107303;107304	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
N2AB	34052	102379;102380;102381	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
N2A	33125	99598;99599;99600	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
N2B	26628	80107;80108;80109	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
Novex-1	26753	80482;80483;80484	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
Novex-2	26820	80683;80684;80685	chr2:178528674;178528673;178528672	chr2:179393401;179393400;179393399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-167
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.3159
• 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
T/K	None	None	0.002	N	0.327	0.178	0.0716867268079	gnomAD-4.0.0	3.18511E-06	None	None	None	None	N	None	0	0	None	0	5.54847E-05	None	0	0	0	0	0
T/P	None	None	0.317	N	0.569	0.351	0.253726318573	gnomAD-4.0.0	1.59245E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	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
T/A	0.1008	likely_benign	0.1032	benign	-0.908	Destabilizing	None	N	0.155	neutral	N	0.479745134	None	None	N
T/C	0.5475	ambiguous	0.5661	pathogenic	-0.565	Destabilizing	0.824	D	0.529	neutral	None	None	None	None	N
T/D	0.4226	ambiguous	0.4337	ambiguous	-0.115	Destabilizing	0.081	N	0.566	neutral	None	None	None	None	N
T/E	0.3142	likely_benign	0.3151	benign	-0.126	Destabilizing	0.081	N	0.539	neutral	None	None	None	None	N
T/F	0.193	likely_benign	0.2042	benign	-1.139	Destabilizing	0.38	N	0.635	neutral	None	None	None	None	N
T/G	0.312	likely_benign	0.3098	benign	-1.133	Destabilizing	0.081	N	0.592	neutral	None	None	None	None	N
T/H	0.204	likely_benign	0.2038	benign	-1.464	Destabilizing	0.824	D	0.59	neutral	None	None	None	None	N
T/I	0.1296	likely_benign	0.1415	benign	-0.405	Destabilizing	0.001	N	0.321	neutral	N	0.480785284	None	None	N
T/K	0.1428	likely_benign	0.1459	benign	-0.577	Destabilizing	0.002	N	0.327	neutral	N	0.478531626	None	None	N
T/L	0.0901	likely_benign	0.0955	benign	-0.405	Destabilizing	0.012	N	0.498	neutral	None	None	None	None	N
T/M	0.0965	likely_benign	0.0998	benign	-0.011	Destabilizing	0.012	N	0.467	neutral	None	None	None	None	N
T/N	0.1361	likely_benign	0.1386	benign	-0.491	Destabilizing	0.081	N	0.507	neutral	None	None	None	None	N
T/P	0.3257	likely_benign	0.3417	ambiguous	-0.542	Destabilizing	0.317	N	0.569	neutral	N	0.481478718	None	None	N
T/Q	0.1871	likely_benign	0.1887	benign	-0.731	Destabilizing	0.38	N	0.576	neutral	None	None	None	None	N
T/R	0.1212	likely_benign	0.1234	benign	-0.354	Destabilizing	0.188	N	0.561	neutral	N	0.480785284	None	None	N
T/S	0.1208	likely_benign	0.1216	benign	-0.828	Destabilizing	None	N	0.13	neutral	N	0.479918493	None	None	N
T/V	0.1276	likely_benign	0.1327	benign	-0.542	Destabilizing	0.012	N	0.467	neutral	None	None	None	None	N
T/W	0.5559	ambiguous	0.56	ambiguous	-1.017	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	N
T/Y	0.2629	likely_benign	0.2713	benign	-0.774	Destabilizing	0.555	D	0.631	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.