TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30651	92176;92177;92178	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
N2AB	29010	87253;87254;87255	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
N2A	28083	84472;84473;84474	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
N2B	21586	64981;64982;64983	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
Novex-1	21711	65356;65357;65358	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
Novex-2	21778	65557;65558;65559	chr2:178549771;178549770;178549769	chr2:179414498;179414497;179414496
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-111
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.763
• 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
P/L	None	None	0.002	N	0.155	0.324	0.524894780827	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
P/S	rs927540266	None	0.01	N	0.12	0.168	0.166414681773	gnomAD-4.0.0	6.16099E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73671E-04	7.1995E-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
P/A	0.0628	likely_benign	0.0628	benign	-0.66	Destabilizing	0.001	N	0.122	neutral	N	0.501205337	None	None	I
P/C	0.4509	ambiguous	0.4399	ambiguous	-0.574	Destabilizing	0.981	D	0.489	neutral	None	None	None	None	I
P/D	0.248	likely_benign	0.2861	benign	-0.451	Destabilizing	0.704	D	0.465	neutral	None	None	None	None	I
P/E	0.1755	likely_benign	0.1972	benign	-0.561	Destabilizing	0.495	N	0.451	neutral	None	None	None	None	I
P/F	0.4732	ambiguous	0.4749	ambiguous	-0.86	Destabilizing	0.893	D	0.504	neutral	None	None	None	None	I
P/G	0.2444	likely_benign	0.2451	benign	-0.821	Destabilizing	0.329	N	0.465	neutral	None	None	None	None	I
P/H	0.1803	likely_benign	0.1811	benign	-0.412	Destabilizing	0.975	D	0.477	neutral	N	0.501264326	None	None	I
P/I	0.2742	likely_benign	0.2626	benign	-0.38	Destabilizing	0.543	D	0.549	neutral	None	None	None	None	I
P/K	0.2117	likely_benign	0.2058	benign	-0.529	Destabilizing	0.495	N	0.452	neutral	None	None	None	None	I
P/L	0.1168	likely_benign	0.1146	benign	-0.38	Destabilizing	0.002	N	0.155	neutral	N	0.50581023	None	None	I
P/M	0.258	likely_benign	0.2455	benign	-0.287	Destabilizing	0.893	D	0.478	neutral	None	None	None	None	I
P/N	0.2022	likely_benign	0.2115	benign	-0.216	Destabilizing	0.704	D	0.497	neutral	None	None	None	None	I
P/Q	0.1301	likely_benign	0.1256	benign	-0.486	Destabilizing	0.828	D	0.491	neutral	None	None	None	None	I
P/R	0.1784	likely_benign	0.1733	benign	0.023	Stabilizing	0.642	D	0.535	neutral	D	0.526045066	None	None	I
P/S	0.0992	likely_benign	0.0995	benign	-0.597	Destabilizing	0.01	N	0.12	neutral	N	0.519521739	None	None	I
P/T	0.0904	likely_benign	0.089	benign	-0.605	Destabilizing	0.01	N	0.12	neutral	N	0.472435649	None	None	I
P/V	0.1711	likely_benign	0.1661	benign	-0.438	Destabilizing	0.329	N	0.464	neutral	None	None	None	None	I
P/W	0.647	likely_pathogenic	0.6444	pathogenic	-0.94	Destabilizing	0.995	D	0.473	neutral	None	None	None	None	I
P/Y	0.4164	ambiguous	0.4193	ambiguous	-0.638	Destabilizing	0.981	D	0.509	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.