TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24914	74965;74966;74967	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
N2AB	23273	70042;70043;70044	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
N2A	22346	67261;67262;67263	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
N2B	15849	47770;47771;47772	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
Novex-1	15974	48145;48146;48147	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
Novex-2	16041	48346;48347;48348	chr2:178571392;178571391;178571390	chr2:179436119;179436118;179436117
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-69
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.7024
• 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/A	rs761941413	-0.135	0.309	N	0.363	0.165	0.231231049324	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	2.00288E-04	4.7E-05	0
T/A	rs761941413	-0.135	0.309	N	0.363	0.165	0.231231049324	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	1.89E-04	0	2.94E-05	0	0
T/A	rs761941413	-0.135	0.309	N	0.363	0.165	0.231231049324	gnomAD-4.0.0	1.85971E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.34492E-04	0	1.27168E-05	0	0
T/I	rs777003046	0.051	0.028	N	0.231	0.18	0.282179105231	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.92E-05	0
T/I	rs777003046	0.051	0.028	N	0.231	0.18	0.282179105231	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
T/I	rs777003046	0.051	0.028	N	0.231	0.18	0.282179105231	gnomAD-4.0.0	1.30168E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7803E-05	0	0
T/S	rs777003046	None	0.034	N	0.092	0.112	0.208816687407	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs777003046	None	0.034	N	0.092	0.112	0.208816687407	gnomAD-4.0.0	6.57722E-06	None	None	None	None	N	None	2.41371E-05	0	None	0	0	None	0	0	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	0.1444	likely_benign	0.127	benign	-0.788	Destabilizing	0.309	N	0.363	neutral	N	0.427339509	None	None	N
T/C	0.5813	likely_pathogenic	0.5169	ambiguous	-0.491	Destabilizing	0.996	D	0.411	neutral	None	None	None	None	N
T/D	0.7133	likely_pathogenic	0.6687	pathogenic	-0.349	Destabilizing	0.742	D	0.401	neutral	None	None	None	None	N
T/E	0.5231	ambiguous	0.4836	ambiguous	-0.391	Destabilizing	0.59	D	0.349	neutral	None	None	None	None	N
T/F	0.4138	ambiguous	0.3475	ambiguous	-1.064	Destabilizing	0.953	D	0.434	neutral	None	None	None	None	N
T/G	0.549	ambiguous	0.4932	ambiguous	-0.985	Destabilizing	0.742	D	0.363	neutral	None	None	None	None	N
T/H	0.467	ambiguous	0.412	ambiguous	-1.321	Destabilizing	0.987	D	0.397	neutral	None	None	None	None	N
T/I	0.2002	likely_benign	0.1713	benign	-0.364	Destabilizing	0.028	N	0.231	neutral	N	0.477594971	None	None	N
T/K	0.2963	likely_benign	0.2533	benign	-0.708	Destabilizing	0.009	N	0.285	neutral	None	None	None	None	N
T/L	0.1334	likely_benign	0.113	benign	-0.364	Destabilizing	0.373	N	0.365	neutral	None	None	None	None	N
T/M	0.112	likely_benign	0.1006	benign	0.059	Stabilizing	0.953	D	0.43	neutral	None	None	None	None	N
T/N	0.2224	likely_benign	0.1974	benign	-0.564	Destabilizing	0.684	D	0.369	neutral	N	0.438030932	None	None	N
T/P	0.155	likely_benign	0.1426	benign	-0.476	Destabilizing	0.939	D	0.435	neutral	N	0.434940272	None	None	N
T/Q	0.3511	ambiguous	0.3055	benign	-0.857	Destabilizing	0.91	D	0.446	neutral	None	None	None	None	N
T/R	0.3099	likely_benign	0.2616	benign	-0.379	Destabilizing	0.59	D	0.414	neutral	None	None	None	None	N
T/S	0.2104	likely_benign	0.1876	benign	-0.814	Destabilizing	0.034	N	0.092	neutral	N	0.47338123	None	None	N
T/V	0.1707	likely_benign	0.1488	benign	-0.476	Destabilizing	0.373	N	0.342	neutral	None	None	None	None	N
T/W	0.8232	likely_pathogenic	0.769	pathogenic	-0.964	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
T/Y	0.4738	ambiguous	0.4133	ambiguous	-0.733	Destabilizing	0.984	D	0.429	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.