Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000756410 | SCV000272149 | uncertain significance | not provided | 2022-03-30 | criteria provided, single submitter | clinical testing | The p.Ala770Thr variant in MYO7A has been reported in 1 Asian individual with adult-onset hearing loss (Ji 2014 PMID: 25342930) and has been identified by our laboratory in 1 Asian individual with features of Usher syndrome who carried pathogenic variants in another gene that were sufficient to explain their disease (LMM data). It has also been identified in 0.06% (11/19272) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). However, this frequency is low enough to be consistent with a recessive allele frequency. This variant has also been reported in ClinVar (Variation ID 229002). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of this variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BP5. |
| ARUP Laboratories, |
RCV000756410 | SCV000884214 | uncertain significance | not provided | 2018-01-23 | criteria provided, single submitter | clinical testing | The p.Ala770Thr variant (rs375253473) has not been reported in the medical literature; however a similar nearby variant (p.Ala771Ser) has been reported in two patients with Usher type I syndrome, one of whom carried a second PCDH15 variant (Nakanishi 2010 and Yoshimura 2014). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.05 percent in the East Asian population (identified on 10 out of 18,616 chromosomes), and has been reported to the ClinVar database with an uncertain classification (Variation ID: 229002). The alanine at position 770 is moderately conserved considering 13 species and computational analyses of the effects of the p.Ala770Thr variant on protein structure and function provide conflicting results (SIFT: damaging, MutationTaster: polymorphism, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Ala770Thr variant with certainty. |
| Labcorp Genetics |
RCV000756410 | SCV001221709 | likely benign | not provided | 2024-08-29 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002503858 | SCV002814155 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2021-12-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000756410 | SCV003762059 | uncertain significance | not provided | 2022-07-29 | criteria provided, single submitter | clinical testing | Identified with additional MYO7A variants in a patient with mild adult-onset hearing loss in published literature (Ji et al., 2014); 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: 25342930) |
| Natera, |
RCV001835732 | SCV002086608 | uncertain significance | Usher syndrome type 1B | 2020-02-02 | no assertion criteria provided | clinical testing |