TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23282	70069;70070;70071	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
N2AB	21641	65146;65147;65148	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
N2A	20714	62365;62366;62367	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
N2B	14217	42874;42875;42876	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
Novex-1	14342	43249;43250;43251	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
Novex-2	14409	43450;43451;43452	chr2:178576288;178576287;178576286	chr2:179441015;179441014;179441013
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-57
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4054
• 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/I	rs876658079	None	0.081	N	0.319	0.167	0.38225645794	gnomAD-4.0.0	2.76242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61581E-06	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
V/A	0.0607	likely_benign	0.0607	benign	-1.545	Destabilizing	None	N	0.138	neutral	N	0.465993898	None	None	N
V/C	0.5604	ambiguous	0.5736	pathogenic	-0.954	Destabilizing	0.883	D	0.452	neutral	None	None	None	None	N
V/D	0.1542	likely_benign	0.1667	benign	-1.4	Destabilizing	0.055	N	0.525	neutral	None	None	None	None	N
V/E	0.1065	likely_benign	0.1143	benign	-1.42	Destabilizing	None	N	0.259	neutral	N	0.417162588	None	None	N
V/F	0.1838	likely_benign	0.193	benign	-1.29	Destabilizing	0.667	D	0.479	neutral	None	None	None	None	N
V/G	0.1119	likely_benign	0.1166	benign	-1.846	Destabilizing	0.042	N	0.532	neutral	N	0.476808325	None	None	N
V/H	0.3516	ambiguous	0.3691	ambiguous	-1.333	Destabilizing	0.667	D	0.567	neutral	None	None	None	None	N
V/I	0.0803	likely_benign	0.079	benign	-0.82	Destabilizing	0.081	N	0.319	neutral	N	0.478616479	None	None	N
V/K	0.144	likely_benign	0.158	benign	-1.184	Destabilizing	0.055	N	0.529	neutral	None	None	None	None	N
V/L	0.1489	likely_benign	0.15	benign	-0.82	Destabilizing	0.042	N	0.305	neutral	N	0.474960098	None	None	N
V/M	0.1191	likely_benign	0.1231	benign	-0.541	Destabilizing	0.859	D	0.399	neutral	None	None	None	None	N
V/N	0.139	likely_benign	0.1416	benign	-0.925	Destabilizing	0.22	N	0.556	neutral	None	None	None	None	N
V/P	0.2089	likely_benign	0.2232	benign	-1.027	Destabilizing	0.364	N	0.55	neutral	None	None	None	None	N
V/Q	0.151	likely_benign	0.1616	benign	-1.151	Destabilizing	0.124	N	0.535	neutral	None	None	None	None	N
V/R	0.1535	likely_benign	0.1669	benign	-0.601	Destabilizing	0.22	N	0.555	neutral	None	None	None	None	N
V/S	0.0939	likely_benign	0.0935	benign	-1.441	Destabilizing	0.055	N	0.504	neutral	None	None	None	None	N
V/T	0.0802	likely_benign	0.0786	benign	-1.357	Destabilizing	0.104	N	0.263	neutral	None	None	None	None	N
V/W	0.7035	likely_pathogenic	0.7342	pathogenic	-1.44	Destabilizing	0.958	D	0.569	neutral	None	None	None	None	N
V/Y	0.4184	ambiguous	0.4365	ambiguous	-1.171	Destabilizing	0.859	D	0.478	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.