TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23191	69796;69797;69798	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
N2AB	21550	64873;64874;64875	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
N2A	20623	62092;62093;62094	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
N2B	14126	42601;42602;42603	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
Novex-1	14251	42976;42977;42978	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
Novex-2	14318	43177;43178;43179	chr2:178576673;178576672;178576671	chr2:179441400;179441399;179441398
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: Fn3-56
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.497
• 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/R	None	None	0.999	N	0.556	0.291	0.391156786388	gnomAD-4.0.0	9.57988E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.2594E-05	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
K/A	0.8205	likely_pathogenic	0.8536	pathogenic	0.017	Stabilizing	0.999	D	0.608	neutral	None	None	None	None	N
K/C	0.9099	likely_pathogenic	0.9403	pathogenic	-0.495	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/D	0.9061	likely_pathogenic	0.9237	pathogenic	-0.309	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/E	0.7567	likely_pathogenic	0.826	pathogenic	-0.323	Destabilizing	0.999	D	0.597	neutral	N	0.485425021	None	None	N
K/F	0.9769	likely_pathogenic	0.9824	pathogenic	-0.339	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/G	0.7728	likely_pathogenic	0.8156	pathogenic	-0.101	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/H	0.5914	likely_pathogenic	0.6673	pathogenic	-0.187	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
K/I	0.9057	likely_pathogenic	0.923	pathogenic	0.243	Stabilizing	1.0	D	0.675	prob.neutral	N	0.468300457	None	None	N
K/L	0.8419	likely_pathogenic	0.8649	pathogenic	0.243	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/M	0.7945	likely_pathogenic	0.8417	pathogenic	-0.143	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/N	0.8585	likely_pathogenic	0.8902	pathogenic	-0.046	Destabilizing	1.0	D	0.715	prob.delet.	N	0.464163081	None	None	N
K/P	0.7974	likely_pathogenic	0.8126	pathogenic	0.19	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
K/Q	0.3936	ambiguous	0.4805	ambiguous	-0.176	Destabilizing	1.0	D	0.711	prob.delet.	N	0.47184931	None	None	N
K/R	0.0871	likely_benign	0.0912	benign	-0.147	Destabilizing	0.999	D	0.556	neutral	N	0.472053079	None	None	N
K/S	0.8243	likely_pathogenic	0.8555	pathogenic	-0.39	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
K/T	0.6533	likely_pathogenic	0.7104	pathogenic	-0.293	Destabilizing	1.0	D	0.659	neutral	N	0.492254993	None	None	N
K/V	0.8664	likely_pathogenic	0.8866	pathogenic	0.19	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
K/W	0.9392	likely_pathogenic	0.9582	pathogenic	-0.458	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/Y	0.9254	likely_pathogenic	0.9428	pathogenic	-0.106	Destabilizing	1.0	D	0.611	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.