TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14171	42736;42737;42738	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
N2AB	12530	37813;37814;37815	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
N2A	11603	35032;35033;35034	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
N2B	5106	15541;15542;15543	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
Novex-1	5231	15916;15917;15918	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
Novex-2	5298	16117;16118;16119	chr2:178633988;178633987;178633986	chr2:179498715;179498714;179498713
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-92
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.6991
• 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
H/Q	rs142842339	None	0.784	N	0.31	0.2	0.0551355673512	gnomAD-4.0.0	6.84363E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15953E-05	0
H/R	rs1288547551	-0.001	0.784	N	0.282	0.237	0.253726318573	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
H/R	rs1288547551	-0.001	0.784	N	0.282	0.237	0.253726318573	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/R	rs1288547551	-0.001	0.784	N	0.282	0.237	0.253726318573	gnomAD-4.0.0	4.95887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78235E-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
H/A	0.1251	likely_benign	0.1931	benign	0.475	Stabilizing	0.3	N	0.267	neutral	None	None	None	None	N
H/C	0.2346	likely_benign	0.2483	benign	0.618	Stabilizing	0.995	D	0.407	neutral	None	None	None	None	N
H/D	0.1059	likely_benign	0.1622	benign	-0.287	Destabilizing	0.6	D	0.353	neutral	N	0.384886102	None	None	N
H/E	0.1594	likely_benign	0.2257	benign	-0.281	Destabilizing	0.495	N	0.255	neutral	None	None	None	None	N
H/F	0.3213	likely_benign	0.3399	benign	0.998	Stabilizing	0.704	D	0.509	neutral	None	None	None	None	N
H/G	0.1873	likely_benign	0.2623	benign	0.257	Stabilizing	0.495	N	0.35	neutral	None	None	None	None	N
H/I	0.2469	likely_benign	0.2932	benign	1.013	Stabilizing	0.543	D	0.414	neutral	None	None	None	None	N
H/K	0.1401	likely_benign	0.1912	benign	0.363	Stabilizing	0.495	N	0.331	neutral	None	None	None	None	N
H/L	0.1014	likely_benign	0.1148	benign	1.013	Stabilizing	0.002	N	0.321	neutral	N	0.360975869	None	None	N
H/M	0.2936	likely_benign	0.362	ambiguous	0.644	Stabilizing	0.893	D	0.439	neutral	None	None	None	None	N
H/N	0.059	likely_benign	0.0749	benign	0.212	Stabilizing	0.784	D	0.26	neutral	N	0.375472796	None	None	N
H/P	0.0624	likely_benign	0.0871	benign	0.856	Stabilizing	0.001	N	0.198	neutral	N	0.283001201	None	None	N
H/Q	0.1055	likely_benign	0.1722	benign	0.276	Stabilizing	0.784	D	0.31	neutral	N	0.384825779	None	None	N
H/R	0.0914	likely_benign	0.1087	benign	-0.143	Destabilizing	0.784	D	0.282	neutral	N	0.411654099	None	None	N
H/S	0.1172	likely_benign	0.1723	benign	0.388	Stabilizing	0.495	N	0.335	neutral	None	None	None	None	N
H/T	0.1432	likely_benign	0.2026	benign	0.483	Stabilizing	0.495	N	0.345	neutral	None	None	None	None	N
H/V	0.1768	likely_benign	0.2304	benign	0.856	Stabilizing	0.329	N	0.333	neutral	None	None	None	None	N
H/W	0.3947	ambiguous	0.4258	ambiguous	0.874	Stabilizing	0.995	D	0.429	neutral	None	None	None	None	N
H/Y	0.1277	likely_benign	0.1262	benign	1.135	Stabilizing	0.784	D	0.307	neutral	N	0.478621272	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.