TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24186	72781;72782;72783	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
N2AB	22545	67858;67859;67860	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
N2A	21618	65077;65078;65079	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
N2B	15121	45586;45587;45588	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
Novex-1	15246	45961;45962;45963	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
Novex-2	15313	46162;46163;46164	chr2:178573576;178573575;178573574	chr2:179438303;179438302;179438301
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: Fn3-63
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7866
• 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	rs768699380	0.197	0.892	N	0.549	0.232	0.311691414656	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	2.16863E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs768699380	0.197	0.892	N	0.549	0.232	0.311691414656	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	2.65316E-04	0	0	0	0	None	0	0	0	0	0
K/E	rs768699380	0.197	0.892	N	0.549	0.232	0.311691414656	gnomAD-4.0.0	1.13497E-05	None	None	None	None	N	None	2.38409E-04	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
K/A	0.757	likely_pathogenic	0.7827	pathogenic	0.07	Stabilizing	0.916	D	0.597	neutral	None	None	None	None	N
K/C	0.8759	likely_pathogenic	0.8832	pathogenic	-0.385	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/D	0.8871	likely_pathogenic	0.8976	pathogenic	-0.174	Destabilizing	0.975	D	0.641	neutral	None	None	None	None	N
K/E	0.7865	likely_pathogenic	0.8054	pathogenic	-0.179	Destabilizing	0.892	D	0.549	neutral	N	0.498447459	None	None	N
K/F	0.9709	likely_pathogenic	0.9743	pathogenic	-0.211	Destabilizing	0.987	D	0.686	prob.neutral	None	None	None	None	N
K/G	0.6342	likely_pathogenic	0.66	pathogenic	-0.08	Destabilizing	0.975	D	0.587	neutral	None	None	None	None	N
K/H	0.4608	ambiguous	0.4822	ambiguous	-0.166	Destabilizing	0.073	N	0.416	neutral	None	None	None	None	N
K/I	0.9157	likely_pathogenic	0.9307	pathogenic	0.383	Stabilizing	0.983	D	0.685	prob.neutral	N	0.496217308	None	None	N
K/L	0.8216	likely_pathogenic	0.8432	pathogenic	0.383	Stabilizing	0.975	D	0.583	neutral	None	None	None	None	N
K/M	0.7578	likely_pathogenic	0.8016	pathogenic	0.002	Stabilizing	0.999	D	0.622	neutral	None	None	None	None	N
K/N	0.7146	likely_pathogenic	0.7634	pathogenic	0.078	Stabilizing	0.967	D	0.675	prob.neutral	N	0.449440004	None	None	N
K/P	0.9393	likely_pathogenic	0.9401	pathogenic	0.304	Stabilizing	0.996	D	0.638	neutral	None	None	None	None	N
K/Q	0.4045	ambiguous	0.4307	ambiguous	-0.066	Destabilizing	0.967	D	0.691	prob.neutral	N	0.48655607	None	None	N
K/R	0.0982	likely_benign	0.0952	benign	-0.036	Destabilizing	0.892	D	0.588	neutral	N	0.466471114	None	None	N
K/S	0.7415	likely_pathogenic	0.7747	pathogenic	-0.315	Destabilizing	0.916	D	0.627	neutral	None	None	None	None	N
K/T	0.6545	likely_pathogenic	0.703	pathogenic	-0.194	Destabilizing	0.983	D	0.641	neutral	N	0.475453254	None	None	N
K/V	0.8489	likely_pathogenic	0.8685	pathogenic	0.304	Stabilizing	0.987	D	0.632	neutral	None	None	None	None	N
K/W	0.9392	likely_pathogenic	0.9457	pathogenic	-0.298	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
K/Y	0.8713	likely_pathogenic	0.8923	pathogenic	0.058	Stabilizing	0.95	D	0.63	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.