Submissions for variant NM_000260.4(MYO7A):c.3134T>C (p.Ile1045Thr)

gnomAD frequency: 0.00005  dbSNP: rs377326213

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000592682	SCV000708439	uncertain significance	not provided	2017-05-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000670848	SCV000795759	uncertain significance	Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2017-11-22	criteria provided, single submitter	clinical testing
Invitae	RCV000592682	SCV001379797	uncertain significance	not provided	2022-09-23	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1045 of the MYO7A protein (p.Ile1045Thr). This variant is present in population databases (rs377326213, gnomAD 0.02%). This missense change has been observed in individual(s) with Usher syndrome (PMID: 17361009). ClinVar contains an entry for this variant (Variation ID: 501914). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000592682	SCV001785514	uncertain significance	not provided	2023-03-30	criteria provided, single submitter	clinical testing	Observed in homozygous state in a patient with Usher syndrome who also harbored a second homozygous variant in the MYO7A gene in the literature (Jaijo et al., 2007); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21311020, 25049390, 17361009, 35836572)
Fulgent Genetics, Fulgent Genetics	RCV002483646	SCV002778690	uncertain significance	Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2021-10-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000592682	SCV002821648	uncertain significance	not provided	2022-10-01	criteria provided, single submitter	clinical testing	MYO7A: PP3
Natera, Inc.	RCV001829681	SCV002086656	uncertain significance	Usher syndrome type 1B	2020-02-20	no assertion criteria provided	clinical testing