TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35629	107110;107111;107112	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
N2AB	33988	102187;102188;102189	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
N2A	33061	99406;99407;99408	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
N2B	26564	79915;79916;79917	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
Novex-1	26689	80290;80291;80292	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
Novex-2	26756	80491;80492;80493	chr2:178528866;178528865;178528864	chr2:179393593;179393592;179393591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-167
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3818
• 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
N/S	rs781094190	-0.062	0.001	N	0.108	0.078	0.0986583533028	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	8.86E-06	0
N/S	rs781094190	-0.062	0.001	N	0.108	0.078	0.0986583533028	gnomAD-4.0.0	9.57799E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69819E-06	1.27524E-04	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
N/A	0.2951	likely_benign	0.2922	benign	-0.345	Destabilizing	0.116	N	0.495	neutral	None	None	None	None	N
N/C	0.5342	ambiguous	0.5321	ambiguous	0.436	Stabilizing	0.944	D	0.6	neutral	None	None	None	None	N
N/D	0.1983	likely_benign	0.1927	benign	-0.062	Destabilizing	0.324	N	0.396	neutral	N	0.473683167	None	None	N
N/E	0.5465	ambiguous	0.519	ambiguous	-0.105	Destabilizing	0.241	N	0.383	neutral	None	None	None	None	N
N/F	0.7471	likely_pathogenic	0.7488	pathogenic	-0.768	Destabilizing	0.818	D	0.629	neutral	None	None	None	None	N
N/G	0.3703	ambiguous	0.374	ambiguous	-0.507	Destabilizing	0.116	N	0.405	neutral	None	None	None	None	N
N/H	0.1758	likely_benign	0.1644	benign	-0.593	Destabilizing	0.773	D	0.515	neutral	N	0.4743766	None	None	N
N/I	0.3601	ambiguous	0.3578	ambiguous	-0.006	Destabilizing	0.627	D	0.613	neutral	N	0.474723317	None	None	N
N/K	0.4186	ambiguous	0.4011	ambiguous	0.148	Stabilizing	0.09	N	0.409	neutral	N	0.4722963	None	None	N
N/L	0.4353	ambiguous	0.4342	ambiguous	-0.006	Destabilizing	0.241	N	0.58	neutral	None	None	None	None	N
N/M	0.5444	ambiguous	0.5427	ambiguous	0.481	Stabilizing	0.818	D	0.584	neutral	None	None	None	None	N
N/P	0.7301	likely_pathogenic	0.7523	pathogenic	-0.093	Destabilizing	0.818	D	0.596	neutral	None	None	None	None	N
N/Q	0.4962	ambiguous	0.4732	ambiguous	-0.341	Destabilizing	0.69	D	0.494	neutral	None	None	None	None	N
N/R	0.4573	ambiguous	0.442	ambiguous	0.242	Stabilizing	0.002	N	0.273	neutral	None	None	None	None	N
N/S	0.0863	likely_benign	0.0893	benign	-0.058	Destabilizing	0.001	N	0.108	neutral	N	0.454924048	None	None	N
N/T	0.1717	likely_benign	0.1708	benign	0.035	Stabilizing	0.001	N	0.125	neutral	N	0.471776225	None	None	N
N/V	0.3447	ambiguous	0.3349	benign	-0.093	Destabilizing	0.241	N	0.607	neutral	None	None	None	None	N
N/W	0.9145	likely_pathogenic	0.9125	pathogenic	-0.753	Destabilizing	0.981	D	0.644	neutral	None	None	None	None	N
N/Y	0.3158	likely_benign	0.3124	benign	-0.481	Destabilizing	0.912	D	0.61	neutral	N	0.474896675	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.