ClinVar Miner

Submissions for variant NM_001145809.2(MYH14):c.4088G>A (p.Arg1363His)

gnomAD frequency: 0.00003  dbSNP: rs727504915
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156300 SCV000206018 uncertain significance not specified 2014-01-02 criteria provided, single submitter clinical testing The Arg1363His variant in MYH14 has not been previously reported in individuals with hearing loss or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugge st that the Arg1363His variant may impact the protein, though this information i s not predictive enough to determine pathogenicity. In summary, additional info rmation is needed to determine the clinical significance of this variant.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375354 SCV001572120 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PP3_Supporting, BS2_Strong
Ambry Genetics RCV003162638 SCV003877552 uncertain significance Inborn genetic diseases 2023-02-09 criteria provided, single submitter clinical testing The c.3965G>A (p.R1322H) alteration is located in exon 29 (coding exon 28) of the MYH14 gene. This alteration results from a G to A substitution at nucleotide position 3965, causing the arginine (R) at amino acid position 1322 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
New York Genome Center RCV003335137 SCV004046552 uncertain significance Autosomal dominant nonsyndromic hearing loss 4A; Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome 2023-04-06 criteria provided, single submitter clinical testing The c.4088G>A p.(Arg1363His) variant identified in MYH14 has not previously been reported in the affected individuals in the literature and it has been deposited in ClinVar [ClinVar ID: 179510] as a Variant of Uncertain Significance (2 submissions). The c.4088G>A variant is observed in 23 out of ~582,722 heterozygous alleles (0.0039% minor allele frequency with 0 homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8). The c.4088G>A variant is located in exon 31 of this 43-exon gene and is predicted to replace a moderately conserved arginine amino acid with histidine at position 1363 in the encoded protein. In silico predictions are not in favor of the damaging effect for the p.(Arg1363His) variant [REVEL = 0.388)]; however, there are no functional studiesto support or refute these predictions. A different missense variant p.(Arg1363Cys) affecting the same amino acid residue has been reported in ClinVar [ClinVar ID:1195791] as a Variant of Uncertain Significance (1 submission).Based on available evidence, this c.4088G>A p.(Arg1363His) variant identified in MYH14 is classified as a Variant of Uncertain Significance.

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