TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23052	69379;69380;69381	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
N2AB	21411	64456;64457;64458	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
N2A	20484	61675;61676;61677	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
N2B	13987	42184;42185;42186	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
Novex-1	14112	42559;42560;42561	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
Novex-2	14179	42760;42761;42762	chr2:178577181;178577180;178577179	chr2:179441908;179441907;179441906
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-55
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3064
• 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
V/A	None	None	0.987	N	0.496	0.374	0.639676494308	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
V/A	0.4655	ambiguous	0.4809	ambiguous	-1.351	Destabilizing	0.987	D	0.496	neutral	N	0.480513499	None	None	N
V/C	0.8178	likely_pathogenic	0.8334	pathogenic	-1.376	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
V/D	0.8673	likely_pathogenic	0.8761	pathogenic	-1.538	Destabilizing	0.999	D	0.725	prob.delet.	D	0.526205436	None	None	N
V/E	0.7336	likely_pathogenic	0.7262	pathogenic	-1.565	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
V/F	0.4266	ambiguous	0.4433	ambiguous	-1.395	Destabilizing	0.998	D	0.617	neutral	N	0.504595689	None	None	N
V/G	0.6194	likely_pathogenic	0.6418	pathogenic	-1.608	Destabilizing	0.999	D	0.711	prob.delet.	D	0.522446454	None	None	N
V/H	0.873	likely_pathogenic	0.8817	pathogenic	-1.183	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
V/I	0.0683	likely_benign	0.07	benign	-0.754	Destabilizing	0.333	N	0.165	neutral	N	0.467244692	None	None	N
V/K	0.6882	likely_pathogenic	0.6852	pathogenic	-1.02	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
V/L	0.3157	likely_benign	0.3294	benign	-0.754	Destabilizing	0.948	D	0.289	neutral	N	0.509651462	None	None	N
V/M	0.2514	likely_benign	0.259	benign	-0.676	Destabilizing	0.999	D	0.538	neutral	None	None	None	None	N
V/N	0.7128	likely_pathogenic	0.7442	pathogenic	-0.911	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/P	0.8161	likely_pathogenic	0.8051	pathogenic	-0.921	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
V/Q	0.6695	likely_pathogenic	0.676	pathogenic	-1.172	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
V/R	0.6441	likely_pathogenic	0.6442	pathogenic	-0.541	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
V/S	0.6169	likely_pathogenic	0.6475	pathogenic	-1.407	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
V/T	0.3813	ambiguous	0.3858	ambiguous	-1.329	Destabilizing	0.996	D	0.455	neutral	None	None	None	None	N
V/W	0.9464	likely_pathogenic	0.9519	pathogenic	-1.516	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/Y	0.8107	likely_pathogenic	0.8406	pathogenic	-1.173	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.