TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24191	72796;72797;72798	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
N2AB	22550	67873;67874;67875	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
N2A	21623	65092;65093;65094	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
N2B	15126	45601;45602;45603	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
Novex-1	15251	45976;45977;45978	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
Novex-2	15318	46177;46178;46179	chr2:178573561;178573560;178573559	chr2:179438288;179438287;179438286
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-63
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2748
• 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	rs1479698498	None	0.892	N	0.43	0.3	0.209622950755	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs1479698498	None	0.892	N	0.43	0.3	0.209622950755	gnomAD-4.0.0	2.00286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.66328E-06	0	0
N/Y	None	None	0.994	N	0.682	0.492	0.430579932962	gnomAD-4.0.0	1.94866E-06	None	None	None	None	N	None	0	0	None	0	2.89805E-05	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
N/A	0.7783	likely_pathogenic	0.8214	pathogenic	-0.991	Destabilizing	0.845	D	0.541	neutral	None	None	None	None	N
N/C	0.5779	likely_pathogenic	0.6423	pathogenic	-0.038	Destabilizing	0.073	N	0.421	neutral	None	None	None	None	N
N/D	0.6967	likely_pathogenic	0.7472	pathogenic	-0.37	Destabilizing	0.981	D	0.534	neutral	N	0.502791128	None	None	N
N/E	0.9078	likely_pathogenic	0.9302	pathogenic	-0.259	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
N/F	0.9324	likely_pathogenic	0.949	pathogenic	-0.671	Destabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
N/G	0.732	likely_pathogenic	0.7572	pathogenic	-1.343	Destabilizing	0.957	D	0.432	neutral	None	None	None	None	N
N/H	0.3814	ambiguous	0.4412	ambiguous	-0.912	Destabilizing	0.994	D	0.654	neutral	D	0.522924616	None	None	N
N/I	0.7803	likely_pathogenic	0.8632	pathogenic	-0.086	Destabilizing	0.967	D	0.699	prob.neutral	N	0.47859726	None	None	N
N/K	0.8896	likely_pathogenic	0.9204	pathogenic	-0.251	Destabilizing	0.983	D	0.648	neutral	N	0.480229845	None	None	N
N/L	0.7725	likely_pathogenic	0.8343	pathogenic	-0.086	Destabilizing	0.95	D	0.677	prob.neutral	None	None	None	None	N
N/M	0.7972	likely_pathogenic	0.8546	pathogenic	0.306	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	N
N/P	0.9748	likely_pathogenic	0.978	pathogenic	-0.358	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
N/Q	0.8283	likely_pathogenic	0.8659	pathogenic	-0.804	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
N/R	0.8588	likely_pathogenic	0.886	pathogenic	-0.257	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
N/S	0.2445	likely_benign	0.2699	benign	-0.947	Destabilizing	0.892	D	0.43	neutral	N	0.508896526	None	None	N
N/T	0.6204	likely_pathogenic	0.7081	pathogenic	-0.634	Destabilizing	0.892	D	0.572	neutral	N	0.438529577	None	None	N
N/V	0.7524	likely_pathogenic	0.836	pathogenic	-0.358	Destabilizing	0.975	D	0.713	prob.delet.	None	None	None	None	N
N/W	0.9683	likely_pathogenic	0.9731	pathogenic	-0.396	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
N/Y	0.6237	likely_pathogenic	0.6661	pathogenic	-0.209	Destabilizing	0.994	D	0.682	prob.neutral	N	0.503298107	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.