TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27086	81481;81482;81483	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
N2AB	25445	76558;76559;76560	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
N2A	24518	73777;73778;73779	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
N2B	18021	54286;54287;54288	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
Novex-1	18146	54661;54662;54663	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
Novex-2	18213	54862;54863;54864	chr2:178564876;178564875;178564874	chr2:179429603;179429602;179429601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-85
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.323
• 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
K/E	None	None	0.001	N	0.253	0.149	0.231873229951	gnomAD-4.0.0	1.59458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43964E-05	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
K/A	0.6166	likely_pathogenic	0.5714	pathogenic	-0.339	Destabilizing	0.272	N	0.506	neutral	None	None	None	None	N
K/C	0.8038	likely_pathogenic	0.7642	pathogenic	-0.601	Destabilizing	0.968	D	0.755	deleterious	None	None	None	None	N
K/D	0.908	likely_pathogenic	0.8898	pathogenic	-0.852	Destabilizing	0.157	N	0.501	neutral	None	None	None	None	N
K/E	0.5018	ambiguous	0.465	ambiguous	-0.801	Destabilizing	0.001	N	0.253	neutral	N	0.464528249	None	None	N
K/F	0.9577	likely_pathogenic	0.95	pathogenic	-0.461	Destabilizing	0.726	D	0.712	prob.delet.	None	None	None	None	N
K/G	0.6436	likely_pathogenic	0.6039	pathogenic	-0.637	Destabilizing	0.272	N	0.562	neutral	None	None	None	None	N
K/H	0.5203	ambiguous	0.5021	ambiguous	-1.146	Destabilizing	0.909	D	0.551	neutral	None	None	None	None	N
K/I	0.8228	likely_pathogenic	0.7987	pathogenic	0.403	Stabilizing	0.667	D	0.718	prob.delet.	N	0.500766893	None	None	N
K/L	0.7783	likely_pathogenic	0.7346	pathogenic	0.403	Stabilizing	0.567	D	0.563	neutral	None	None	None	None	N
K/M	0.6279	likely_pathogenic	0.5694	pathogenic	0.491	Stabilizing	0.968	D	0.543	neutral	None	None	None	None	N
K/N	0.8059	likely_pathogenic	0.781	pathogenic	-0.553	Destabilizing	0.497	N	0.457	neutral	N	0.472240931	None	None	N
K/P	0.9021	likely_pathogenic	0.893	pathogenic	0.186	Stabilizing	0.726	D	0.547	neutral	None	None	None	None	N
K/Q	0.2882	likely_benign	0.2606	benign	-0.813	Destabilizing	0.331	N	0.498	neutral	N	0.481813264	None	None	N
K/R	0.0786	likely_benign	0.0695	benign	-0.496	Destabilizing	0.001	N	0.155	neutral	N	0.486195812	None	None	N
K/S	0.719	likely_pathogenic	0.6771	pathogenic	-1.027	Destabilizing	0.272	N	0.451	neutral	None	None	None	None	N
K/T	0.6079	likely_pathogenic	0.5633	ambiguous	-0.806	Destabilizing	0.497	N	0.511	neutral	N	0.473037398	None	None	N
K/V	0.7688	likely_pathogenic	0.719	pathogenic	0.186	Stabilizing	0.567	D	0.602	neutral	None	None	None	None	N
K/W	0.9205	likely_pathogenic	0.9055	pathogenic	-0.416	Destabilizing	0.968	D	0.744	deleterious	None	None	None	None	N
K/Y	0.884	likely_pathogenic	0.8683	pathogenic	-0.017	Destabilizing	0.726	D	0.682	prob.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.